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

NCT ID: NCT04504435

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-29
• Study Completion Date: 2024-01-11

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.

Conditions

Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Participants in Cohort 1

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.

Group Type: EXPERIMENTAL

GSK3494245

Intervention Type: DRUG

Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.

Placebo

Intervention Type: DRUG

Matching placebo capsules will be provided

Participants in Cohort 2

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.

Group Type: EXPERIMENTAL

GSK3494245

Intervention Type: DRUG

Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.

Placebo

Intervention Type: DRUG

Matching placebo capsules will be provided

Cohort 3: Participants receiving GSK3494245 (fasted then fed)

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.

Group Type: EXPERIMENTAL

GSK3494245

Intervention Type: DRUG

Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.

Cohort 3: Participants receiving GSK3494245 (fed then fasted)

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.

Group Type: EXPERIMENTAL

GSK3494245

Intervention Type: DRUG

Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.

Interventions

GSK3494245

Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.

Intervention Type: DRUG

Placebo

Matching placebo capsules will be provided

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 to <=50 years of age, at the time of signing the informed consent.

Exclusion Criteria

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

Other Identifiers

2019-004492-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

208441

Identifier Type: -

Identifier Source: org_study_id