Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability and PK profile of single and repeat ascending doses of GSK3186899 in healthy subjects. This is a Phase 1 first time in human study, to investigate the effect of food on PK of GSK3186899. This study will consists of two parts. Part A (dose escalation phase) will be a single ascending, sequential cross-over design in cohorts 1, 2 and 3 of subjects. Cohort 1 and 2 will be 4-way cross-over which includes 4 dosing regimens of GSK3186899 and placebo (3:1 ratio) under fasted conditions. Cohort 3 will be 2-way cross-over which includes 2 treatment periods, 2 dosing regimens in fasted and fed conditions. In Part B (repeat dose escalation phase) subjects will be randomized to receive repeat doses of either GSK3186899 or placebo (3:1 ratio) in either fed or fasted conditions. Part B will be conducted based on the review of all safety, tolerability and PK data from Part A. The study duration includes screening, treatment periods and follow-up.


Eligibility Criteria:
Inclusion Criteria

* Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
* 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 subject 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 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m\^2) (inclusive).
* Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP).
* Capable of giving signed informed consent.

Exclusion Criteria

* History or presence of or current 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.
* Previous history of leishmaniasis.
* ALT \>1.5\* upper limit of normal (ULN).
* Bilirubin \>1.5\*ULN (isolated bilirubin \>1.5\*ULN is acceptable if bilirubin is fractionated and direct bilirubin \<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 past history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).
* ECG QT interval corrected for heart rate (QTc) \>450 milliseconds (msec).
* Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton-pump inhibitors (PPIs) or anti-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.
* Participation in the study 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.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates participation in the study.
* Regular use of known drugs of abuse.
* Subjects with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate glomerular filtration rate (GFR) \<=80 (mL/minute/1.73m\^2).
* Presence of Hepatitis B surface antigen (HBsAg) or Positive Hepatitis C antibody test result at screening.
* Positive human immunodeficiency virus (HIV) antibody test.
* Positive pre-study drug/alcohol screen.
* 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.
* Part A (Food effect) Cohort 3 only: Subject must have no dietary restrictions (example, lactose intolerance) or inability to eat an adapted standard meal (includes 35-40 percent fat content).
* Part A (Food effect) Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (example, cholelithiasis) within 14 days prior to receiving the study treatment.
* Part B only: Early morning cortisol \<420 nanomoles per liter (nmol/L) and inadequate response (rise of \<250 millimoles per liter (mmol/L) from Baseline) to adrenocorticotropic hormone (ACTH) stimulation test at Day -1.