A Study to Compare the Pharmacokinetics (PK) of GSK2982772 Following Administration of Different Modified Release (MR) Formulations in Capsule and MR Tablet Formulations Relative to an Immediate Release (IR) Tablet Formulation and to Check the PK of MR Formulation in Capsule Following Repeat Doses

A Three Part, Non-randomized, Open Label Study Designed to Assess the Pharmacokinetics of GSK2982772 Following Administration of Minitab Modified Release Formulations in a Capsule Relative to an Immediate Release Reference Tablet Formulation (Part A), the Pharmacokinetics of Escalating, Repeat Doses of a Selected Minitab Modified Release Prototype (Part B) , and the Pharmacokinetics of GSK2982772 Following Administration of Modified Release Tablet Formulations in the Fed and Fasted State (Part C) in Healthy Participants

GSK2982772 is a first-in-class, highly selective, receptor-interacting protein-1 (RIP1) kinase inhibitor being developed for the treatment of inflammatory bowel disease, plaque psoriasis (PsO), rheumatoid arthritis (RA) and other disease conditions. PK data from the first time in human (FTIH) study for GSK2982772 showed that the half life of GSK2982772 was short (approximately 2 to 3 hours). A once daily (QD) formulation would be more convenient from a subject perspective and could offer the advantage of providing a flatter GSK2982772 concentration time profile. Following completion of Parts A and B, it was determined that the slowest minitab formulation provided a PK profile suitable for QD dosing but this formulation was susceptible to a food effect. This study will evaluate the pharmacokinetics of GSK2982772 following administration of different minitab MR formulations in a capsule relative to an IR reference tablet formulation, the pharmacokinetics of selected MR formulation in capsule following repeat doses for 3 days and to compare the pharmacokinetics of GSK2982772 following administration of MR tablet formulations in the fed and fasted state relative to an IR tablet formulation. The study is divided into three parts: Part A will be a non-randomized 6 periods, sequential, 6-way fixed sequence design in which up to 4 MR minitab formulations in a capsule will be evaluated. Periods 1, 2, and 3 will evaluate a slow MR release duration (nominally 24 hours), a fast MR release duration (nominally 10 hours), and IR tablet respectively. Periods 4, 5 and 6 will have flexible dose regimen and it will depend on the outcomes of Period 1 to 3. Subjects will be admitted to the clinic the previous day before dosing. Each in-patient period will consist of 3 days and 2 nights followed by a minimum washout period of 7 days between doses, for both Part A and C. In Part A and C, 16 healthy subjects will be enrolled such that at least 12 evaluable subjects complete the study. Part B will be an open-label, repeat dose study in which the selected MR minitab formulation in capsule will be evaluated. Each in-patient period will consist of 5 days and 4 nights. There will be a minimum of 7 days washout period between the last morning dose of one period and the first dose of the next period. In Part B, 10 healthy subjects will be enrolled such that at least 6 evaluable subjects complete the study. Part C of the study will be a non-randomised 6 period, sequential, fixed sequence crossover design in which MR tablet formulations will be evaluated. Periods 1 and 2 will evaluate single dose administration of a 240 milligram (mg) MR tablet and the 240 mg IR tablet (reference), respectively. Periods 3, 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 and 2.

Inclusion Criteria:

• Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Body weight greater than and equal to 50 kilogram (kg) and body mass index within the range 19.0 to 32.0 kilogram per meter square (kg/m^2) (inclusive).
• A male subject must agree to use a highly effective 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, not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive during the treatment period and for at least 30 days before and 30 days after the last dose of study treatment.
• Capable of giving signed informed consent.

Exclusion Criteria:

• History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), 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.
• Parts A and C only: Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
• Part B only: Subjects with current history of suicidal ideation behavior as measured using the columbia-suicide severity rating scale (C-SSRS) or a history of attempted suicide.
• History of clinically significant psychiatric disorders as judged by the investigator. Depression requiring treatment in the last 2 years.
• History of herpes zoster (shingles) reactivation.
• History or diagnosis of obstructive sleep apnea.
• History of a significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
• History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
• A positive diagnostic tuberculosis (TB) test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
• History of GI surgery (with exception of appendectomy).
• History of cholecystectomy or gall stones.
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
• ALT greater than 1.5 times upper limit of normal (ULN).
• Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage of total).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
• Corrected QT interval (QTc) greater than 450 millisecond (msec).
• Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen [up to 2 gram (g) per day], hormone replacement therapy and hormonal contraception are permitted).
• Live or attenuated vaccine(s) within 30 days of enrolment, or plans to receive such vaccines during the study or plans to receive a vaccine within 30 days + 5 half-lives of the last dose of study medication.
• Subject in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56 day period; therefore donation or loss of greater than 400 mL of blood within the previous 3 months.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrolment or past participation within the last 3 months before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
• Subjects who have previously been enrolled in this study. Subjects in Part A of this study are not permitted to participate in Part B. Subjects in Parts A or B of this study are not permitted to participate in Part C.
• Current or history of renal disease or estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation calculation less than 60 mL/minutes(min)/1.73m^2 at screening.
• Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
• An elevated C-reactive protein (CRP) outside the normal reference range.
• Part B only: A positive anti-nuclear antibody (ANA) outside the normal reference range.
• Confirmed positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5 years.
• Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Current use or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening. A carbon monoxide breath test reading of greater than 10 parts per million (ppm).
• 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 0-00 capsules as part of study participation.
• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening.
• Total cholesterol greater than or equal to 300 milligram/deciliter (mg/dL) (greater than or equal to 7.77 millimoles per liter [mmol]/L]) or triglycerides greater than or equal to 250 mg/dL (greater than or equal to 2.82 mmol/L).
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee.