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

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.


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.