A Safety and Pharmacokinetic (PK) Study of GSK2982772 in Healthy Subjects

This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. This study will also assess the impact of food during the repeat doses of GSK2982772. This will be a two part study; Part A and Part B. Part A (cohort 1) - single ascending dose, randomized, placebo-controlled, 3-way crossover. Part B (cohorts 2, 3, 4 and 5) - repeat dose, randomized, placebo-controlled, sequential-group. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in crossover manner on Day 1 of each of the three periods in Part A. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohort 2 of Part B and in 9:5 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohorts 3, 4 and 5 of Part B. Approximately 66 subjects will be included in this study. The study duration, including screening and follow-up, will not be expected to exceed 13 weeks for Part A and 8 weeks for Part B.


Eligibility Criteria:
Inclusion Criteria:

* Subject must be 18 to 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 (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 19 - 30 kg per square meter (kg/m\^2) (inclusive).
* 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 pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance for a minimum of 28 days prior to the treatment period and for at least 30 days after the last administration of study drug. A WOCBP using a hormonal method of highly effective contraception must also agree to partner use of a male condom during the treatment period and for at least 30 days after the last administration of study drug.
* 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.
* History of herpes zoster (shingles) reactivation.
* Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration \>5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
* ALT \>1.5 times upper limit of normal (ULN).
* Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN 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).
* ECG QT interval corrected for heart rate (QTc) \>450 millisecond (msec).
* History of serious or recurrent infections or has had an active infection within 14 days of receiving study medication.
* History of diagnosis of obstructive sleep apnoea or significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
* Part A: History of active suicidal ideation behavior (SIB) within the past 6 months or any history of attempted suicide in a subject's lifetime.
* History of current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
* Past or intended use of over-the-counter or prescription medication, including herbal medications, 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.
* Subject received a vaccine (either live attenuated or now-live) within 30 days prior to randomization, or plans to receive a live attenuated vaccine within 30 days + 5 half-lives (32 days) of the last dose of study medication.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (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).
* Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV1 and 2) antibody test.
* Regular use of known drugs of abuse.
* Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKS-EPI) Creatinine \> 1.6 mg/deciliter (mg/dL) with an age appropriate glomerular filtration rate (GFR) \<= 60 (mL/minute/1.73 m\^2) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
* An elevated C-reactive protein (CRP) outside of the normal reference range.
* Regular alcohol consumption within 6 months prior to the study defined as: For United Kingdom (UK) - an average weekly intake of \>14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Cotinine or carbon monoxide levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Unwilling or unable to swallow multiple size 00 capsules as part of study participation.

PART B Specific exclusion criteria:

* History of SIB as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide.
* A positive anti-nuclear antibody (ANA) outside of the normal reference range.
* Fasting total cholesterol \>=300 mg/dL or triglycerides \>=250 mg/dL.