Dataset from 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.