Dataset from A Two Part, Non-randomised, Open Label Study Designed to Assess the Pharmacokinetic Profile of Modified Release Prototype Coated Tablet Formulations of GSK2982772 Relative to an Immediate Release Reference Tablet Formulation at a Fixed Strength (Part A) and the Pharmacokinetic Profile of Alternative Tablet Strengths of the Selected Modified Release Prototype Coated Tablet Formulation (Part B, Optional) in Healthy Participants

Previous clinical studies of immediate release (IR) formulations of GSK2982772 resulted in a
high peak to trough ratio of GSK2982772. Additionally, the short half-life for GSK2982772
(approximately 2 to 3 hours) necessitates twice a daily (BID) or thrice daily (TID) dosing of
an IR formulation. As a result, MR formulations using a polymer matrix approach with
minitablets in capsule and MR tablet formulations were investigated. The emerging PK data of
the MR formulations investigated to date have demonstrated that a once daily (QD) PK profile
can be achieved in the fasted state but the polymer matrix formulation is susceptible to food
effects when administered with a high fat breakfast. The purpose of this study is to evaluate
MR prototype coated tablet formulations. This study will evaluate the PK of MR prototype
coated tablet formulations of GSK2982772. The study is divided into two parts; Part A and
Part B. The MR tablet coating used in Part A and the initial periods of Part B will have an
aperture drilled into the enteric coating of either side of the tablet. This allows some drug
release to commence in the stomach whilst providing controlled release throughout the
gastrointestinal (GI) tract. In Part B only, a new investigational medicinal product (IMP)
will be manufactured to allow comparison of the tablet coating either with apertures (i.e.,
drilled) or without apertures (i.e., full coat/non drilled). Part A will be a 6-period, 6-way
fixed sequence design, up to 4 MR tablet prototype coated formulations will be evaluated in
fasted state at 240 milligrams (mg). Periods 1, 2 and 3 will evaluate MR1, IR tablet and MR2
respectively. Periods 4, 5 and 6 will be flexible and the dosing regimen will be dependent on
the outcome of Periods 1 to 3. In addition, the impact of food (high fat meal, standard
breakfast or administration 30 or 60 minutes before a standard breakfast) on selected MR
prototype coated tablet formulations may also be evaluated in Period 4, 5 or 6 of Part A.
Each inpatient period for MR regimens (Periods 1, 3, 4 to 6) will consist of 4 days and 3
nights, and the inpatient period for the IR tablet (Period 2) will consist of 3 days and 2
nights. There will be a minimum washout of 7 days between doses, and a follow-up visit will
occur at 7 to 9 days after the last study treatment. The Part B of the study will be a
7-period fixed sequence which will evaluate the selected MR prototype coated tablet
formulation(s) at different tablet strengths or as multiple unit doses and with or without
apertures in the tablet coatings. There will be an interim review after each period 1 to 5 of
Part B to select the dose level, formulation and prandial status for each subsequent period.
An interim data review after Part B Period 6 will determine if optional Period 7 is required
and the dose level, dosing time (morning or evening), formulation and prandial status for
that period. Each inpatient period will consist of a 4-day and 3-night with a minimum of 7
days washout between doses. A follow-up visit will occur at 7 to 9 days after the last study
treatment. Approximately 33 subjects will be enrolled in the study. The total duration for
Part A will be approximately 10-12 weeks and 10-14 weeks for Part B (including screening
period of approximately 4 weeks).