search
Back to results

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants

Primary Purpose

Leishmaniasis

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK3494245
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leishmaniasis focused on measuring GSK3494245, Leishmaniasis, Single Ascending Dose, First Time in Human, Pharmacokinetics

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria

  • Participant must be 18 to <=50 years of age, at the time of signing the informed consent.
  • Participant must be healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 Kilograms (kg) and body mass index (BMI) within the range 18.5-28 Kilograms per meter square (kg/m^2) (inclusive).
  • Male participants only. A male participant with a female partner of reproductive potential must agree to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and protocol.

Exclusion Criteria

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • Abnormal blood pressure, as determined by the investigator.
  • Previous history of leishmaniasis.
  • Alanine aminotransferase (ALT) greater than 1.5 times upper limit of normal (ULN).
  • Total bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than 35 percent [%]).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Current or history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).
  • Consumption of greater than 14 units/week alcohol (male volunteers).
  • Current or history of change in taste or smell without any plausible clinical explanation based on investigator's clinical judgement.
  • QTc greater than 450 milliseconds (msec) based on average of triplicate ECGs.
  • Waveform abnormalities including premature ventricular contraction (PVC) triplets and more than 500 single PVCs in 24 hours, or any other abnormalities at the discretion of investigator.
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
  • Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton pump inhibitors (PPIs) or anti-histamine 2 receptor (H2) antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped to <=2 grams/day).
  • Participation in the study that would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
  • Current enrollment or past participation in this clinical study.
  • Participants with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate Glomerular filtration rate (GFR) <90 (milliliter per minute per 1.73 meter square [mL/min/1.73m^2]).
  • Screening urine albumin:creatinine ratio >30 milligram per gram (mg/g) (>3 milligram per millimole [mg/mmol])
  • Presence of hepatitis B surface antigen (HBsAg) test result at screening.
  • Positive hepatitis C antibody test result at screening.
  • Positive hepatitis C Ribonucleic acid (RNA) test result at screening.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Presence of clinically significant hematuria and/or proteinuria.
  • Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening.
  • Positive pre-study drug/alcohol screen.
  • Regular use of known drugs of abuse.
  • Food Effect Cohort 3 only: Participant must have no dietary restrictions (e.g., lactose intolerance) or inability to eat gelatin or an adapted standard meal (includes 35-40% fat content).
  • Food Effect Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (e.g. cholelithiasis) within 14 days prior to receiving the study treatment.
  • Participants must not have travelled to an area (as determined by the investigator) with a high prevalence of leishmanial/parasitic infections in the 6 months before screening or intend to do so in the 3 months after the final dose of study treatment.
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.
  • A positive laboratory confirmation of corona virus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.

Sites / Locations

  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Participants in Cohort 1

Participants in Cohort 2

Cohort 3: Participants receiving GSK3494245 (fasted then fed)

Cohort 3: Participants receiving GSK3494245 (fed then fasted)

Arm Description

Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.

Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.

Participants will receive the selected dose level (DLX) of GSK3494245 in the fasted state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fed state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.

Participants will receive the DLX of GSK3494245 in the fed state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fasted state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
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. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Number of participants with treatment emergent AEs and SAEs
Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.
Number of participants with clinically significant abnormal findings in hematology parameters
Blood samples will be collected for the assessment of hematology parameters.
Number of participants with clinically significant abnormal findings in clinical chemistry parameters
Blood samples will be collected for the assessment of chemistry parameters
Number of participants with urinalysis findings
Urine samples will be collected for the assessment of urinalysis parameters.
Number of participants with clinically significant abnormal findings in vital signs
Number of participants with abnormal vital signs will be assessed.
Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters
Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.
Number of participants with abnormal cardiac telemetry findings
Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.

Secondary Outcome Measures

Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition
Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.
AUC (0-t) of GSK3494245 following single dose administration under fed condition
Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.
AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition
Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.
AUC (0-inf) of GSK3494245 following single dose administration under fed condition
Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.
Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.
Cmax of GSK3494245 following single dose administration under fed condition
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.
Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition
Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.
Tmax of GSK3494245 following single dose administration under fed condition
Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.
Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition
Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
t1/2 of GSK3494245 following single dose administration under fed condition
Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration
Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.
Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration
Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245
Renal Clearance (CLr) of GSK3494245 following single dose administration
Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.
Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245
Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.
Dose-proportionality assessment using Cmax following single dose of GSK3494245
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.

Full Information

First Posted
August 5, 2020
Last Updated
August 4, 2023
Sponsor
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT04504435
Brief Title
Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants
Official Title
A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 in Healthy Participants
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 29, 2020 (Actual)
Primary Completion Date
June 14, 2024 (Anticipated)
Study Completion Date
June 14, 2024 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH) study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of a single ascending dose (SAD), crossover design where each participant will receive a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period, according to the randomization schedule in a blinded manner. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1 regimen under fed then fasted conditions in a 1:1 ratio. The fed conditions will investigate the effect of safety, tolerability and PK of a single dose of GSK3494245 following food administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leishmaniasis
Keywords
GSK3494245, Leishmaniasis, Single Ascending Dose, First Time in Human, Pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
The study will consist of 3 cohorts (Cohorts 1, 2 and 3), conducted in sequential order. Cohorts 1 and 2 will consist of a single dose, ascending, crossover design. Cohorts 1-2 will comprise of a 4-way crossover which includes 4 dosing regimens under fasted conditions. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed condition and 1 regimen under fed then fasted condition in a 1:1 ratio.
Masking
ParticipantInvestigator
Masking Description
This will be a double-blind study with respect to allocation of GSK3494245 or placebo to participants. The food effect part of the study will be open label.
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants in Cohort 1
Arm Type
Experimental
Arm Description
Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
Arm Title
Participants in Cohort 2
Arm Type
Experimental
Arm Description
Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
Arm Title
Cohort 3: Participants receiving GSK3494245 (fasted then fed)
Arm Type
Experimental
Arm Description
Participants will receive the selected dose level (DLX) of GSK3494245 in the fasted state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fed state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
Arm Title
Cohort 3: Participants receiving GSK3494245 (fed then fasted)
Arm Type
Experimental
Arm Description
Participants will receive the DLX of GSK3494245 in the fed state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fasted state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
Intervention Type
Drug
Intervention Name(s)
GSK3494245
Intervention Description
Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsules will be provided
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
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. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with treatment emergent AEs and SAEs
Description
Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with clinically significant abnormal findings in hematology parameters
Description
Blood samples will be collected for the assessment of hematology parameters.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with clinically significant abnormal findings in clinical chemistry parameters
Description
Blood samples will be collected for the assessment of chemistry parameters
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with urinalysis findings
Description
Urine samples will be collected for the assessment of urinalysis parameters.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with clinically significant abnormal findings in vital signs
Description
Number of participants with abnormal vital signs will be assessed.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters
Description
Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.
Time Frame
Up to 14 days post last dose in each treatment period
Title
Number of participants with abnormal cardiac telemetry findings
Description
Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.
Time Frame
Up to 24 hours post dose on Day 1
Secondary Outcome Measure Information:
Title
Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition
Description
Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
AUC (0-t) of GSK3494245 following single dose administration under fed condition
Description
Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.
Time Frame
Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition
Description
Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
AUC (0-inf) of GSK3494245 following single dose administration under fed condition
Description
Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.
Time Frame
Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition
Description
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Cmax of GSK3494245 following single dose administration under fed condition
Description
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.
Time Frame
Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition
Description
Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Tmax of GSK3494245 following single dose administration under fed condition
Description
Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.
Time Frame
Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition
Description
Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
t1/2 of GSK3494245 following single dose administration under fed condition
Description
Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Time Frame
Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration
Description
Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration
Description
Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Renal Clearance (CLr) of GSK3494245 following single dose administration
Description
Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245
Description
Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
Title
Dose-proportionality assessment using Cmax following single dose of GSK3494245
Description
Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.
Time Frame
Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
A male participant with a female partner of reproductive potential must agree to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
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 18 to <=50 years of age, at the time of signing the informed consent. Participant must be healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Body weight >=50 Kilograms (kg) and body mass index (BMI) within the range 18.5-28 Kilograms per meter square (kg/m^2) (inclusive). Male participants only. A male participant with a female partner of reproductive potential must agree to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and protocol. Exclusion Criteria History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data. Abnormal blood pressure, as determined by the investigator. Previous history of leishmaniasis. Alanine aminotransferase (ALT) greater than 1.5 times upper limit of normal (ULN). Total bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than 35 percent [%]). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Current or history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID). Consumption of greater than 14 units/week alcohol (male volunteers). Current or history of change in taste or smell without any plausible clinical explanation based on investigator's clinical judgement. QTc greater than 450 milliseconds (msec) based on average of triplicate ECGs. Waveform abnormalities including premature ventricular contraction (PVC) triplets and more than 500 single PVCs in 24 hours, or any other abnormalities at the discretion of investigator. Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome. Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton pump inhibitors (PPIs) or anti-histamine 2 receptor (H2) antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped to <=2 grams/day). Participation in the study that would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research. Current enrollment or past participation in this clinical study. Participants with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate Glomerular filtration rate (GFR) <90 (milliliter per minute per 1.73 meter square [mL/min/1.73m^2]). Screening urine albumin:creatinine ratio >30 milligram per gram (mg/g) (>3 milligram per millimole [mg/mmol]) Presence of hepatitis B surface antigen (HBsAg) test result at screening. Positive hepatitis C antibody test result at screening. Positive hepatitis C Ribonucleic acid (RNA) test result at screening. Positive human immunodeficiency virus (HIV) antibody test. Presence of clinically significant hematuria and/or proteinuria. Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening. Positive pre-study drug/alcohol screen. Regular use of known drugs of abuse. Food Effect Cohort 3 only: Participant must have no dietary restrictions (e.g., lactose intolerance) or inability to eat gelatin or an adapted standard meal (includes 35-40% fat content). Food Effect Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (e.g. cholelithiasis) within 14 days prior to receiving the study treatment. Participants must not have travelled to an area (as determined by the investigator) with a high prevalence of leishmanial/parasitic infections in the 6 months before screening or intend to do so in the 3 months after the final dose of study treatment. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study. A positive laboratory confirmation of corona virus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
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
Cambridge
ZIP/Postal Code
CB2 2GG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com

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

Learn more about this trial

Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants

We'll reach out to this number within 24 hrs