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Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)

Primary Purpose

Urinary Tract Infections

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gepotidacin
Placebo matching nitrofurantoin
Nitrofurantoin
Placebo matching gepotidacin
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Tract Infections focused on measuring Acute cystitis, Efficacy, Gepotidacin, Nitrofurantoin, Urinary Tract Infection, Simple cystitis

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • The participant is >=12 years of age at the time of signing the informed consent/assent and has a body weight >=40 kilogram (kg).
  • The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset <96 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain.
  • The participant has nitrite or pyuria (greater than [>]15 white blood cell [WBC]/high-power field [HPF]) or the presence of 3 plus (+)/large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
  • The participant is female.
  • The participant is capable of giving signed informed consent/assent.

Exclusion Criteria:

  • The participant resides in a nursing home or dependent care type-facility.
  • The participant has a body mass index >=40.0 kilogram per meter square (kg/m^2) or a body mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes.
  • The participant has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
  • The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.

  • The participant has any of the following:

    1. Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe pain,; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; Or
    2. Known acute porphyria.
    3. Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention .
  • The participant has a known glucose-6 phosphate dehydrogenase deficiency.
  • The participant has a serious underlying disease that could be imminently life threatening, or the participant is unlikely to survive for the duration of the study period.
  • The participant has acute cystitis that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or Enterobacterales (other than Escherichia coli) as the contributing pathogen.
  • The participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments or preclude complete resolution of acute cystitis symptoms.
  • The participant has an anatomical or physiological anomaly that predisposes the participant to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease (for example [e.g.], polycystic renal disease), or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency).
  • The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
  • The participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptom onset >=96 hours before study entry, or a temperature >=101.4 degree Fahrenheit (>=38 Degrees Celsius [C]), flank pain, chills, or any other manifestations suggestive of upper UTI.
  • The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance <60 milliliters per minute (mL/min) or clinically significant elevated serum creatinine as determined by the investigator).
  • The participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
  • The participant has congenital long QT syndrome or known prolongation of the QTc interval.
  • The participant has uncompensated heart failure.
  • The participant has severe left ventricular hypertrophy.
  • The participant has a family history of QT prolongation or sudden death.
  • The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months.
  • The participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (TdP) per the www.crediblemeds.org. "Known Risk of TdP" category at the time of her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor.
  • For any participant >=12 to <18 years of age, the participant has an abnormal ECG reading.
  • The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle-branch block.
  • The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
  • The participant has a known ALT value >2 times upper limit of normal (ULN).
  • The participant has a known bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
  • The participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.
  • The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
  • The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.

Sites / Locations

  • GSK Investigational Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Gepotidacin

Nitrofurantoin

Arm Description

Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo BID; approximately every 12 hours for 5 days.

Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.

Outcomes

Primary Outcome Measures

Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set)
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline [BL] to <10^3 colony forming units per milliliter [CFU/mL] without receiving other systemic antimicrobials [AB] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no symptoms without receiving other AB before the TOC visit [or AB for uUTI on day of TOC visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline [BL] to <10^3 colony forming units per milliliter [CFU/mL] without receiving other systemic antimicrobials [AB] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit [or AB for uUTI on day of TOC visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

Secondary Outcome Measures

Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in total symptom score (CSS) from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.
Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population
Participant-level MOs at TOC were categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.
Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population
Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP)s had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
TR at FU was categorized as therapeutic success and therapeutic failure. A therapeutic success at FU referred to participants who have been deemed both a microbiological success (reduction of all QUPs recovered at BL to <10^3 CFU/mL, following microbiological eradication at the TOC visit, without receiving other AB before the FU visit) and a clinical success (resolution of signs and symptoms of acute cystitis demonstrated at the TOC visit persist at the FU visit and no new signs and symptoms, without receiving other AB before the FU visit [or AB for uUTI on day of FU visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Clinical outcomes at FU were categorized as SCR, DCR, CI, CW, CR and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at the TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. Unable to determine outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for the current infection (uUTI) prior to the assessment (unless CS or CR outcome criteria were met).
Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Participant-level MOs at FU were categorized as sustained microbiological eradication (SME), microbiological recurrence (MR), microbiological persistence (MP), delayed microbiological eradication (DME) and unable to determine (UTD). SME at FU was defined as all baseline QUPs had an outcome of sustained eradication at FU (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the FU Visit). MR at FU was defined as at least one QUP had an outcome of recurrence (≥10^3 CFU/mL) and none had an outcome of persistence at FU. MP at FU was defined as at least one QUP had an outcome of persistence at FU. DME at FU was defined as at least one QUP had an outcome of delayed eradication and none had an outcome of persistence or recurrence at FU. UTD at FU was defined as all QUP outcomes were unable to determine at FU.
Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Participant- level microbiological response at FU was categorized as microbiological success and microbiological failure. Microbiological success at FU was defined as all baseline QUPs had a microbiological outcome of sustained eradication at FU visit. Microbiological failure at FU was defined as not meeting criteria of microbiological success including those participants with UTD outcome.
Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in CSS from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure.
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Clinical outcomes at FU were categorized as Sustained Clinical Response (SCR), Delayed Clinical Response (DCR), CI, CW, Clinical Recurrence (CR) and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. UTD outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for current infection (uUTI) prior to assessment (unless CS or CR outcome criteria were met).
Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Number of Participants With Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Change From Baseline in Hematology Parameters: Neutrophil Count, Lymphocyte Count, Monocyte Count, Eosinophil Count, Basophil Count and Platelet Count at On Therapy and Test of Cure Visit
Blood samples were collected for the analysis of hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Hematology Parameter: Hemoglobin Level
Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Hematology Parameter: Hematocrit Level
Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count
Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Number of Participants With Urinalysis Dipstick Results
Urine samples were collected for urinalysis: Urine Glucose (GLU), Urine Protein (PRO), Urine Occult Blood (BLO), Urine Ketones (KET), Urine Nitrite (NIT) and Urine Leukocyte Esterase (LEU). Baseline is defined as the latest pre-dose assessment with a non-missing value. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Trace, Small, Moderate, Large, Positive, 50 milligram per deciliter (mg/dL), 150 mg/dL, >=500 mg/dL, 30 mg/dL, 100 mg/dL, 200 mg/dL, 5 mg/dL, 20 mg/dL, >=80 mg/dL indicating concentrations in the urine sample. In the row title (GLU, Baseline, Negative), GLU indicates parameter, Baseline is the visit and Negative indicates the concentration in the urine sample. Data is presented in similar way for others parameters.
Absolute Mean Values of Urine Specific Gravity
Urine samples were collected from participants to assess urine specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Absolute Mean Values of Urine Potential of Hydrogen (pH)
Urine samples were collected from participants to assess urine pH levels. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit
SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit
Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Change From Baseline in Body Temperature
Temperature was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter: QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Worst-case Post-baseline
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450, >450 to <=480, >480 to <=500 millisecond (msec) are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter- QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF) at Worst-case Post-baseline
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450 msec, >450 msec to <=480 msec are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.

Full Information

First Posted
December 3, 2019
Last Updated
July 15, 2023
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT04187144
Brief Title
Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)
Official Title
A Phase III, Randomized, Multicenter, Parallel-Group, Double-Blind, Double-Dummy Study in Adolescent and Adult Female Participants Comparing the Efficacy and Safety of Gepotidacin to Nitrofurantoin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 23, 2020 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
December 1, 2022 (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
Yes

5. Study Description

Brief Summary
The study will be conducted to evaluate the therapeutic response (combined per participant microbiological and clinical response) of oral gepotidacin compared to oral nitrofurantoin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections
Keywords
Acute cystitis, Efficacy, Gepotidacin, Nitrofurantoin, Urinary Tract Infection, Simple cystitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1606 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gepotidacin
Arm Type
Experimental
Arm Description
Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo BID; approximately every 12 hours for 5 days.
Arm Title
Nitrofurantoin
Arm Type
Active Comparator
Arm Description
Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.
Intervention Type
Drug
Intervention Name(s)
Gepotidacin
Intervention Description
Gepotidacin will be available as tablets at a unit dose strength of 750mg. Participants will administer two 750 mg tablets, BID. Each dose will be taken with water after consumption of food.
Intervention Type
Drug
Intervention Name(s)
Placebo matching nitrofurantoin
Intervention Description
Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Participants will administer 1 capsule BID. Each dose should be taken with water after consumption of food.
Intervention Type
Drug
Intervention Name(s)
Nitrofurantoin
Intervention Description
Nitrofurantoin will be available as over-encapsulated 100 mg capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Participants will administer one 100 mg capsule, BID. Each dose should be taken with water after consumption of food.
Intervention Type
Drug
Intervention Name(s)
Placebo matching gepotidacin
Intervention Description
Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Participants will administer two tablets, BID. Each dose should be taken with water after consumption of food.
Primary Outcome Measure Information:
Title
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set)
Description
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline [BL] to <10^3 colony forming units per milliliter [CFU/mL] without receiving other systemic antimicrobials [AB] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no symptoms without receiving other AB before the TOC visit [or AB for uUTI on day of TOC visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population
Description
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline [BL] to <10^3 colony forming units per milliliter [CFU/mL] without receiving other systemic antimicrobials [AB] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit [or AB for uUTI on day of TOC visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Time Frame
TOC visit (Days 9 to 16)
Secondary Outcome Measure Information:
Title
Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population
Description
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in total symptom score (CSS) from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population
Description
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population
Description
Participant-level MOs at TOC were categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.
Time Frame
TOC Visit (Days 9 to 16)
Title
Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population
Description
Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP)s had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description
TR at FU was categorized as therapeutic success and therapeutic failure. A therapeutic success at FU referred to participants who have been deemed both a microbiological success (reduction of all QUPs recovered at BL to <10^3 CFU/mL, following microbiological eradication at the TOC visit, without receiving other AB before the FU visit) and a clinical success (resolution of signs and symptoms of acute cystitis demonstrated at the TOC visit persist at the FU visit and no new signs and symptoms, without receiving other AB before the FU visit [or AB for uUTI on day of FU visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description
Clinical outcomes at FU were categorized as SCR, DCR, CI, CW, CR and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at the TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. Unable to determine outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for the current infection (uUTI) prior to the assessment (unless CS or CR outcome criteria were met).
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description
Participant-level MOs at FU were categorized as sustained microbiological eradication (SME), microbiological recurrence (MR), microbiological persistence (MP), delayed microbiological eradication (DME) and unable to determine (UTD). SME at FU was defined as all baseline QUPs had an outcome of sustained eradication at FU (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the FU Visit). MR at FU was defined as at least one QUP had an outcome of recurrence (≥10^3 CFU/mL) and none had an outcome of persistence at FU. MP at FU was defined as at least one QUP had an outcome of persistence at FU. DME at FU was defined as at least one QUP had an outcome of delayed eradication and none had an outcome of persistence or recurrence at FU. UTD at FU was defined as all QUP outcomes were unable to determine at FU.
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description
Participant- level microbiological response at FU was categorized as microbiological success and microbiological failure. Microbiological success at FU was defined as all baseline QUPs had a microbiological outcome of sustained eradication at FU visit. Microbiological failure at FU was defined as not meeting criteria of microbiological success including those participants with UTD outcome.
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population
Description
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in CSS from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population
Description
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure.
Time Frame
TOC visit (Days 9 to 16)
Title
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Description
Clinical outcomes at FU were categorized as Sustained Clinical Response (SCR), Delayed Clinical Response (DCR), CI, CW, Clinical Recurrence (CR) and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. UTD outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for current infection (uUTI) prior to assessment (unless CS or CR outcome criteria were met).
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Description
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
Time Frame
FU visit (Days 21 to 31)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Time Frame
From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Time Frame
From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)
Title
Change From Baseline in Hematology Parameters: Neutrophil Count, Lymphocyte Count, Monocyte Count, Eosinophil Count, Basophil Count and Platelet Count at On Therapy and Test of Cure Visit
Description
Blood samples were collected for the analysis of hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Hematology Parameter: Hemoglobin Level
Description
Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Hematology Parameter: Hematocrit Level
Description
Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count
Description
Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Description
Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Description
Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels
Description
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels
Description
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels
Description
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels
Description
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Number of Participants With Urinalysis Dipstick Results
Description
Urine samples were collected for urinalysis: Urine Glucose (GLU), Urine Protein (PRO), Urine Occult Blood (BLO), Urine Ketones (KET), Urine Nitrite (NIT) and Urine Leukocyte Esterase (LEU). Baseline is defined as the latest pre-dose assessment with a non-missing value. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Trace, Small, Moderate, Large, Positive, 50 milligram per deciliter (mg/dL), 150 mg/dL, >=500 mg/dL, 30 mg/dL, 100 mg/dL, 200 mg/dL, 5 mg/dL, 20 mg/dL, >=80 mg/dL indicating concentrations in the urine sample. In the row title (GLU, Baseline, Negative), GLU indicates parameter, Baseline is the visit and Negative indicates the concentration in the urine sample. Data is presented in similar way for others parameters.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Absolute Mean Values of Urine Specific Gravity
Description
Urine samples were collected from participants to assess urine specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Absolute Mean Values of Urine Potential of Hydrogen (pH)
Description
Urine samples were collected from participants to assess urine pH levels. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit
Description
SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit
Description
Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Change From Baseline in Body Temperature
Description
Temperature was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Title
Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter: QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Worst-case Post-baseline
Description
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450, >450 to <=480, >480 to <=500 millisecond (msec) are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Time Frame
Up to Day 31
Title
Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter- QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF) at Worst-case Post-baseline
Description
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450 msec, >450 msec to <=480 msec are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Time Frame
Up to Day 31

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The participant is >=12 years of age at the time of signing the informed consent/assent and has a body weight >=40 kilogram (kg). The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset <96 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain. The participant has nitrite or pyuria (greater than [>]15 white blood cell [WBC]/high-power field [HPF]) or the presence of 3 plus (+)/large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures. The participant is female. The participant is capable of giving signed informed consent/assent. Exclusion Criteria: The participant resides in a nursing home or dependent care type-facility. The participant has a body mass index >=40.0 kilogram per meter square (kg/m^2) or a body mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes. The participant has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation. The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications. The participant has any of the following: Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe pain,; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; Or Known acute porphyria. Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention . The participant has a known glucose-6 phosphate dehydrogenase deficiency. The participant has a serious underlying disease that could be imminently life threatening, or the participant is unlikely to survive for the duration of the study period. The participant has acute cystitis that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or Enterobacterales (other than Escherichia coli) as the contributing pathogen. The participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments or preclude complete resolution of acute cystitis symptoms. The participant has an anatomical or physiological anomaly that predisposes the participant to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease (for example [e.g.], polycystic renal disease), or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency). The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract. The participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptom onset >=96 hours before study entry, or a temperature >=101.4 degree Fahrenheit (>=38 Degrees Celsius [C]), flank pain, chills, or any other manifestations suggestive of upper UTI. The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance <60 milliliters per minute (mL/min) or clinically significant elevated serum creatinine as determined by the investigator). The participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease). The participant has congenital long QT syndrome or known prolongation of the QTc interval. The participant has uncompensated heart failure. The participant has severe left ventricular hypertrophy. The participant has a family history of QT prolongation or sudden death. The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months. The participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (TdP) per the www.crediblemeds.org. "Known Risk of TdP" category at the time of her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor. For any participant >=12 to <18 years of age, the participant has an abnormal ECG reading. The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle-branch block. The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months. The participant has a known ALT value >2 times upper limit of normal (ULN). The participant has a known bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]). The participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice. The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
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
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
GSK Investigational Site
City
Homewood
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
GSK Investigational Site
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
GSK Investigational Site
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85296
Country
United States
Facility Name
GSK Investigational Site
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381-3689
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85015-1104
Country
United States
Facility Name
GSK Investigational Site
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
GSK Investigational Site
City
Modesto
State/Province
California
ZIP/Postal Code
95350-5365
Country
United States
Facility Name
GSK Investigational Site
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
GSK Investigational Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
Facility Name
GSK Investigational Site
City
Valencia
State/Province
California
ZIP/Postal Code
91355-5319
Country
United States
Facility Name
GSK Investigational Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20011
Country
United States
Facility Name
GSK Investigational Site
City
Apollo Beach
State/Province
Florida
ZIP/Postal Code
33572
Country
United States
Facility Name
GSK Investigational Site
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33435
Country
United States
Facility Name
GSK Investigational Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33761
Country
United States
Facility Name
GSK Investigational Site
City
Coconut Creek
State/Province
Florida
ZIP/Postal Code
33063
Country
United States
Facility Name
GSK Investigational Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
GSK Investigational Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
GSK Investigational Site
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33461
Country
United States
Facility Name
GSK Investigational Site
City
Leesburg
State/Province
Florida
ZIP/Postal Code
34748
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33186-2178
Country
United States
Facility Name
GSK Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32810
Country
United States
Facility Name
GSK Investigational Site
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
GSK Investigational Site
City
Palm Springs
State/Province
Florida
ZIP/Postal Code
33406
Country
United States
Facility Name
GSK Investigational Site
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33026-4383
Country
United States
Facility Name
GSK Investigational Site
City
Plant City
State/Province
Florida
ZIP/Postal Code
33563
Country
United States
Facility Name
GSK Investigational Site
City
Sweetwater
State/Province
Florida
ZIP/Postal Code
33172
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
GSK Investigational Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
Facility Name
GSK Investigational Site
City
Blackfoot
State/Province
Idaho
ZIP/Postal Code
83221
Country
United States
Facility Name
GSK Investigational Site
City
Boise
State/Province
Idaho
ZIP/Postal Code
83704
Country
United States
Facility Name
GSK Investigational Site
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
GSK Investigational Site
City
Hanover
State/Province
Maryland
ZIP/Postal Code
21076
Country
United States
Facility Name
GSK Investigational Site
City
Fall River
State/Province
Massachusetts
ZIP/Postal Code
02723
Country
United States
Facility Name
GSK Investigational Site
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
GSK Investigational Site
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
Facility Name
GSK Investigational Site
City
East Orange
State/Province
New Jersey
ZIP/Postal Code
07018-1502
Country
United States
Facility Name
GSK Investigational Site
City
Lawrenceville
State/Province
New Jersey
ZIP/Postal Code
08648
Country
United States
Facility Name
GSK Investigational Site
City
Mount Laurel
State/Province
New Jersey
ZIP/Postal Code
08054
Country
United States
Facility Name
GSK Investigational Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10456
Country
United States
Facility Name
GSK Investigational Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11229
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016-7313
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
GSK Investigational Site
City
Cary
State/Province
North Carolina
ZIP/Postal Code
27518
Country
United States
Facility Name
GSK Investigational Site
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28412
Country
United States
Facility Name
GSK Investigational Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
GSK Investigational Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58104
Country
United States
Facility Name
GSK Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45215
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43231
Country
United States
Facility Name
GSK Investigational Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45424
Country
United States
Facility Name
GSK Investigational Site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
Facility Name
GSK Investigational Site
City
Bala-Cynwyd
State/Province
Pennsylvania
ZIP/Postal Code
19004
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
GSK Investigational Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
GSK Investigational Site
City
Lancaster
State/Province
South Carolina
ZIP/Postal Code
29720
Country
United States
Facility Name
GSK Investigational Site
City
Union
State/Province
South Carolina
ZIP/Postal Code
29379
Country
United States
Facility Name
GSK Investigational Site
City
Milan
State/Province
Tennessee
ZIP/Postal Code
38358
Country
United States
Facility Name
GSK Investigational Site
City
New Tazewell
State/Province
Tennessee
ZIP/Postal Code
37824-1409
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78735
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78744 -1645
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77087
Country
United States
Facility Name
GSK Investigational Site
City
Katy
State/Province
Texas
ZIP/Postal Code
77450
Country
United States
Facility Name
GSK Investigational Site
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75149
Country
United States
Facility Name
GSK Investigational Site
City
Missouri City
State/Province
Texas
ZIP/Postal Code
77459
Country
United States
Facility Name
GSK Investigational Site
City
North Richland Hills
State/Province
Texas
ZIP/Postal Code
76180
Country
United States
Facility Name
GSK Investigational Site
City
Plano
State/Province
Texas
ZIP/Postal Code
75024
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78251
Country
United States
Facility Name
GSK Investigational Site
City
Bountiful
State/Province
Utah
ZIP/Postal Code
84010
Country
United States
Facility Name
GSK Investigational Site
City
Saint George
State/Province
Utah
ZIP/Postal Code
84790
Country
United States
Facility Name
GSK Investigational Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
GSK Investigational Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
GSK Investigational Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
Facility Name
GSK Investigational Site
City
Maroubra
State/Province
New South Wales
ZIP/Postal Code
2035
Country
Australia
Facility Name
GSK Investigational Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
GSK Investigational Site
City
Tarragindi
State/Province
Queensland
ZIP/Postal Code
4121
Country
Australia
Facility Name
GSK Investigational Site
City
Gabrovo
ZIP/Postal Code
5300
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Haskovo
ZIP/Postal Code
6300
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Kyustendil
ZIP/Postal Code
2500
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Montana
ZIP/Postal Code
3400
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Ruse
ZIP/Postal Code
7000
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Shumen
ZIP/Postal Code
9700
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Stara Zagora
ZIP/Postal Code
6000
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Targovisthe
ZIP/Postal Code
7700
Country
Bulgaria
Facility Name
GSK Investigational Site
City
Aurangabad
ZIP/Postal Code
431001
Country
India
Facility Name
GSK Investigational Site
City
Chandrapur
ZIP/Postal Code
442402
Country
India
Facility Name
GSK Investigational Site
City
Hyderabad
ZIP/Postal Code
500004
Country
India
Facility Name
GSK Investigational Site
City
Mumbai
ZIP/Postal Code
400022
Country
India
Facility Name
GSK Investigational Site
City
Nagpur
ZIP/Postal Code
440003
Country
India
Facility Name
GSK Investigational Site
City
Nagpur
ZIP/Postal Code
440015
Country
India
Facility Name
GSK Investigational Site
City
Nashik
ZIP/Postal Code
422101
Country
India
Facility Name
GSK Investigational Site
City
New Delhi
ZIP/Postal Code
110062
Country
India
Facility Name
GSK Investigational Site
City
Pune
ZIP/Postal Code
411016
Country
India
Facility Name
GSK Investigational Site
City
Rajkot
ZIP/Postal Code
360005
Country
India
Facility Name
GSK Investigational Site
City
Surat
ZIP/Postal Code
395010
Country
India
Facility Name
GSK Investigational Site
City
Ansan-si
ZIP/Postal Code
15355
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Goyang-si, Gyeonggi-do
ZIP/Postal Code
10326
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Hwasun-gun, Jeollanam-do
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Seoul
ZIP/Postal Code
06973
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Suwon
ZIP/Postal Code
16247
Country
Korea, Republic of
Facility Name
GSK Investigational Site
City
Katowice
ZIP/Postal Code
40-748
Country
Poland
Facility Name
GSK Investigational Site
City
Ostrowiec Swietokrzyski
ZIP/Postal Code
27-400
Country
Poland
Facility Name
GSK Investigational Site
City
Swidnik
ZIP/Postal Code
21-040
Country
Poland
Facility Name
GSK Investigational Site
City
Warszawa
ZIP/Postal Code
02798
Country
Poland

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
Citations:
PubMed Identifier
36271314
Citation
Perry C, Hossain M, Powell M, Raychaudhuri A, Scangarella-Oman N, Tiffany C, Xu S, Dumont E, Janmohamed S. Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants. Infect Dis Ther. 2022 Dec;11(6):2297-2310. doi: 10.1007/s40121-022-00706-9. Epub 2022 Oct 21.
Results Reference
derived
PubMed Identifier
36255258
Citation
Fishman C, Caverly Rae JM, Posobiec LM, Laffan SB, Lerman SA, Pearson N, Janmohamed S, Dumont E, Nunn-Floyd D, Stanislaus DJ. Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0048322. doi: 10.1128/aac.00483-22. Epub 2022 Oct 18.
Results Reference
derived
PubMed Identifier
34978887
Citation
Scangarella-Oman NE, Hossain M, Hoover JL, Perry CR, Tiffany C, Barth A, Dumont EF. Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0149221. doi: 10.1128/AAC.01492-21. Epub 2022 Jan 3.
Results Reference
derived

Learn more about this trial

Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)

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