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Drug-drug Interaction Study of Gepotidacin

Primary Purpose

Infections, Bacterial

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gepotidacin
Cimetidine
Rifampicin
Midazolam
Digoxin
Placebo matching to gepotidacin
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infections, Bacterial focused on measuring Gepotidacin, Drug Interaction, Pharmacokinetic, Safety, Bacterial Infection, Japanese Healthy Adults

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Participant must be greater than or equal to (>=) 18 to less than or equal to (=<) 50 years of age inclusive, at the time of signing the informed consent.
  • Participants who are healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead ECG results. A participant with clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired).

The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview.

The participant has been living outside of Japan for up to 10 years as confirmed by interview.

  • Participants have a body weight >=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
  • Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    1. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit.

The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion Criteria:

  • Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator's opinion may place the participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (GI), respiratory, hematologic, or immunologic disease.
  • Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator.
  • Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
  • Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
  • Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. difficile toxin test.
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or has a positive drug screen at Screening or upon admission to the clinic.
  • History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
  • Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin.
  • Use of any systemic antibiotic within 30 days of screening.
  • Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of <=2 grams/day), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up Visit, unless, in the opinion of the investigator and Sponsor, the medication will not interfere with the study. Any exceptions will be discussed with the Sponsor or Medical Monitor on a case-by-case basis and the reasons will be documented.
  • Previous exposure to gepotidacin.
  • Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer).
  • Past participation in this clinical study.
  • Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) at Screening or Check-in.
  • Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
  • Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Screening or Check-in.
  • History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance <=90 milliliters per minute (mL/min).
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • History of regular alcohol consumption within 6 months of Screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.
  • Cohort 3 Only: Digoxin-related exclusions include the following at Screening:

Serum potassium >5.5 milliequivalent per liter (mEq/L) or < 3.6 mEq/L Serum magnesium <1.6 milligrams per deciliter (mg/dL) Serum calcium (total) <8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.

  • Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
  • Participant is unable to comply with all study procedures, in the opinion of the investigator.
  • Participant should not participate in the study, in the opinion of the investigator or Sponsor.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg

Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mg

Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mg

Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mg

Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fed

Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fed

Cohort 4: Placebo fed then fasted then fed

Arm Description

This is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine.

This is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin.

Participants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.

Participants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.

Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.

Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.

Cohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo.

Outcomes

Primary Outcome Measures

Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 2: Cmax of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: Tmax of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: AUC(0-t) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Cmax of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Tlag of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Cohort 3: Tmax of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-t) of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: AUC(0-infinity) of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Cmax of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Tlag of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Cohort 3: Tmax of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-t) of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: AUC(0-infinity) of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Secondary Outcome Measures

Cohort 1: AUC (0-24) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: AUC(0-48) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: Tlag of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 1: AUC(0-24) of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 1: AUC(0-48) of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 1: Renal Clearance (CLr) of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).
Cohort 1: Number of Participants With SAE and Non-SAE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Cohort 2: AUC(0-24) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: AUC(0-48) of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: T1/2 of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: Vz/F of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: CL/F of Gepotidacin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 2: Ae Total of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 2: AUC(0-24) of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 2: AUC(0-48) of Gepotidacin in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 2: CLr of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 2: Ae(t1-t2) of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Cohort 2: Number of Participants With SAE and Non-SAE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: T1/2 of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Vz/F of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: CL/F of Digoxin in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Cmin of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: T1/2 of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Vz/F of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: CL/F of Midazolam in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 3: Number of Participants With SAE and Non-SAE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.
Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Full Information

First Posted
July 28, 2020
Last Updated
December 9, 2021
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT04493931
Brief Title
Drug-drug Interaction Study of Gepotidacin
Official Title
A Pharmacokinetic, Multi-cohort Study in Healthy Adult Subjects to Assess Gepotidacin as Victim and as Perpetrator of Drug-Drug Interactions Via CYP450, Renal and Intestinal Transporters, and to Assess Gepotidacin Pharmacokinetics in Japanese Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
August 14, 2020 (Actual)
Primary Completion Date
December 21, 2020 (Actual)
Study Completion Date
December 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Bacterial
Keywords
Gepotidacin, Drug Interaction, Pharmacokinetic, Safety, Bacterial Infection, Japanese Healthy Adults

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Cohort 1 and 2 are open-label, fixed sequence DDI cohorts. Cohort 3 is an open-label, 2-sequence, 2-period crossover randomized DDI cohort. Cohort 4 is a double-blind, placebo-controlled, randomized sequence study to investigate the safety and PK of gepotidacin.
Masking
ParticipantInvestigator
Masking Description
Cohort 1 to 3 are open-label cohorts. Cohort 4 is a double-blind cohort which contains blinded treatment of gepotidacin and placebo.
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Arm Type
Experimental
Arm Description
This is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine.
Arm Title
Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Arm Type
Experimental
Arm Description
This is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin.
Arm Title
Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mg
Arm Type
Experimental
Arm Description
Participants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.
Arm Title
Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mg
Arm Type
Experimental
Arm Description
Participants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.
Arm Title
Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fed
Arm Type
Experimental
Arm Description
Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.
Arm Title
Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fed
Arm Type
Experimental
Arm Description
Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.
Arm Title
Cohort 4: Placebo fed then fasted then fed
Arm Type
Placebo Comparator
Arm Description
Cohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo.
Intervention Type
Drug
Intervention Name(s)
Gepotidacin
Other Intervention Name(s)
GSK2140944
Intervention Description
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Cimetidine
Intervention Description
Cimetidine tablets will be available as unit dose strength 400 mg and will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Rifampicin
Intervention Description
Rifampicin Capsules will be available as unit dose strength 300 mg and will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally.
Intervention Type
Drug
Intervention Name(s)
Digoxin
Intervention Description
Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally.
Intervention Type
Other
Intervention Name(s)
Placebo matching to gepotidacin
Intervention Description
Placebo matching to gepotidacin tablets will be administered orally.
Primary Outcome Measure Information:
Title
Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Cmax of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Tmax of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: AUC(0-t) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Cmax of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tlag of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tmax of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-t) of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-infinity) of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Cmax of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tlag of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tmax of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-t) of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-infinity) of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
Description
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Time Frame
Up to 22 days
Title
Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 22 days
Title
Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 22 days
Title
Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 22 days
Title
Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 22 days
Title
Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval
Description
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.
Time Frame
Up to 22 days
Title
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Secondary Outcome Measure Information:
Title
Cohort 1: AUC (0-24) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: AUC(0-48) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Tlag of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Title
Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Title
Cohort 1: AUC(0-24) of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2
Title
Cohort 1: AUC(0-48) of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Title
Cohort 1: Renal Clearance (CLr) of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Title
Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Time Frame
0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2
Title
Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Title
Cohort 1: Number of Participants With SAE and Non-SAE
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Time Frame
Up to 17 days
Title
Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 17 days
Title
Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 17 days
Title
Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 17 days
Title
Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 17 days
Title
Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
Description
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Time Frame
Up to 17 days
Title
Cohort 2: AUC(0-24) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: AUC(0-48) of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: T1/2 of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Vz/F of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: CL/F of Gepotidacin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Ae Total of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: AUC(0-24) of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: AUC(0-48) of Gepotidacin in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: CLr of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Ae(t1-t2) of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Time Frame
0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 2: Number of Participants With SAE and Non-SAE
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Time Frame
Up to 26 days
Title
Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 26 days
Title
Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 26 days
Title
Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 26 days
Title
Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 26 days
Title
Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
Description
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Time Frame
Up to 26 days
Title
Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: T1/2 of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Vz/F of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: CL/F of Digoxin in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Cmin of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: T1/2 of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Vz/F of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: CL/F of Midazolam in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 3: Number of Participants With SAE and Non-SAE
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Time Frame
Up to 30 days
Title
Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 30 days
Title
Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 30 days
Title
Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 30 days
Title
Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
Description
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Time Frame
Up to 30 days
Title
Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
Description
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
Time Frame
Up to 30 days
Title
Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State
Description
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Title
Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Title
Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3
Title
Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3
Title
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Title
Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State
Description
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Other Pre-specified Outcome Measures:
Title
Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Description
Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted.
Time Frame
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participant must be greater than or equal to (>=) 18 to less than or equal to (=<) 50 years of age inclusive, at the time of signing the informed consent. Participants who are healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead ECG results. A participant with clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired). The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview. The participant has been living outside of Japan for up to 10 years as confirmed by interview. Participants have a body weight >=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m^2) (inclusive). Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Exclusion Criteria: Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator's opinion may place the participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (GI), respiratory, hematologic, or immunologic disease. Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator. Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic. Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures. Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. difficile toxin test. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). History of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or has a positive drug screen at Screening or upon admission to the clinic. History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation. Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin. Use of any systemic antibiotic within 30 days of screening. Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of <=2 grams/day), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up Visit, unless, in the opinion of the investigator and Sponsor, the medication will not interfere with the study. Any exceptions will be discussed with the Sponsor or Medical Monitor on a case-by-case basis and the reasons will be documented. Previous exposure to gepotidacin. Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer). Past participation in this clinical study. Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) at Screening or Check-in. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention. Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in. Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Screening or Check-in. History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance <=90 milliliters per minute (mL/min). A positive test for human immunodeficiency virus (HIV) antibody. History of regular alcohol consumption within 6 months of Screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine. Cohort 3 Only: Digoxin-related exclusions include the following at Screening: Serum potassium >5.5 milliequivalent per liter (mEq/L) or < 3.6 mEq/L Serum magnesium <1.6 milligrams per deciliter (mg/dL) Serum calcium (total) <8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in. Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period. Participant is unable to comply with all study procedures, in the opinion of the investigator. Participant should not participate in the study, in the opinion of the investigator or Sponsor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com

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Drug-drug Interaction Study of Gepotidacin

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