A Safety and Tolerability Study of GSK2982772, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Male Subjects

This study is the first administration of GSK2982772 in humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of single and repeat oral doses of up to 14 days with GSK2982772 in healthy male subjects.

This study is planned to include approximately 52 subjects and will consist of 2 parts: Part A - single ascending dose, randomized, placebo controlled, 4 way crossover. In addition to the crossover treatment periods, up to 8 subjects in cohort 2 will participate in an additional treatment period and receive GSK2982772 with a high-fat meal. Part B - repeat dose, randomized, placebo controlled, sequential-group. In both cohorts of Part A (Cohorts 1 and 2), subjects will be randomized equally (1:1:1:1) to one of 4 treatment sequences. Within each period, allocation of active to placebo treatment will be 3:1.

In all cohorts in Part B (Cohorts 3, 4 and 5) subjects will be randomized to GSK2982772 or placebo in a 3:1 ratio. If required, subjects in the additional cohorts in Part A (Cohort 6) and Part B (Cohort 7) will be randomized to GSK2982772 or placebo in a 1:1:1:1 and 3:1 ratio, respectively. The study duration, including screening and follow-up, is not expected to exceed 105 days for any subject in the study.


Eligibility Criteria:
Inclusion Criteria:

* Male subjects between 18 and 65 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, neurological 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 reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Note: Screened subjects with laboratory values outside of the normal range may be repeated once for inclusion into the study at the discretion of the Investigator.
* Body weight \>= 50 kilogram (kg) and body mass index (BMI) within the range 19 - 30 (kilogram/squared meter) kg/m\^2 (inclusive).
* Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until at least five half-lives of study medication after the last dose of study medication or the follow-up visit, whichever is longer. a. Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b. Vasectomy with documentation of azoospermia; c. Male condom plus partner use of one of the contraceptive options: Contraceptive subdermal implant that meets the standard operation procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone. Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository). These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and as explained by the investigator.

Exclusion Criteria:

* Alanine aminotransferase (ALT) and bilirubin \>1.5x Upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* History of active infections within 14 days of receiving study medication.
* Average QT duration corrected for heart rate by Fridericia's formula (QTcF) \> 450 milliseconds (msec) of three measures taken at least 5 minutes apart in the semi-supine position.
* History or diagnosis of obstructive sleep apnoea.
* History of a significant respiratory disorder.
* History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
* Unable to refrain from prescription or non-prescription drugs, including agents active in the central nervous system, vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and throughout the study, unless in the opinion of the Investigator and/or GlaxoSmithKline Medical Monitor (if needed) the medication will not interfere with the study procedures or compromise subject safety.
* History of regular alcohol consumption within 6 months of the study, defined as: For United Kingdom (UK) - an average weekly intake of \>21 units for males. One unit is equivalent to 8 gram(g) of alcohol: a half-pint (approximately 240 millilitre \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Current use or history of regular tobacco- or nicotine-containing product use within 6 months of screening. Subject must have urinary cotinine levels indicative of non-smoking status at screening visit.
* Unwilling or unable to swallow multiple size 00 capsules as part of study participation
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator and/or Medical Monitor (if appropriate), contraindicates their participation.
* Subject received a vaccine (either live attenuated or non-live) within 30 days of randomization OR plan to receive a live attenuated vaccine within 30 days + 5 half-lives of the last dose of study medication.
* Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine \> 1.6 milligram/decilitre (mg/dL) with an age appropriate glomerular filtration rate (GFR) \<=60 (millilitre/minute \[mL/min\]/1.73 squared meter \[m\^2\]) estimated by the CKD-EPI equation.
* A positive anti-nuclear antibody (ANA) or elevated C-reactive protein (CRP) outside of the normal reference range.
* Peripheral capillary oxygen saturation (SpO2) \< 95% at room air.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
* A positive pre-study drug/alcohol screen.
* A positive test for Human Immunodeficiency Virus (HIV) antibody.
* A positive tuberculosis test.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
* 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).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Part B Specific Exclusion Criteria:

* Total cholesterol \>=300 mg/dL or triglycerides \>=250 mg/dL. - Subjects who, in the Investigator/designee's judgment, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires (e.g., type 4 or 5 on the Columbia Suicide Severity Rating Scale \[C-SSRS\] in the last 5 years).
* For Cohort 5 Only (or another Cohort where Entero Test is to be performed) - History of gall bladder surgery or gall bladder removal, or history of an acute disease state (e.g., cholelithiasis) within 14 days of receiving study medication.