A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772

Summary

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).

Conditions

• Autoimmune Diseases

Interventions

DRUG

GSK2982772 Modified Release

GSK2982772 MR will be available as MR prototype coated tablet with unit dose strength of 240 mg in Part A. In Part B, GSK2982772 MR prototype coated tablet with unit dose strength of 120 mg (may be changed following interim review of Part B) will be administered by subjects. GSK2982772 MR will be administered orally with 240 milliliter (mL) of water.

DRUG

GSK2982772 Immediate Release

In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water

Sponsors & Collaborators

• Quotient Sciences

  collaborator INDUSTRY

• GlaxoSmithKline

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · GlaxoSmithKline

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-09-26

Primary Completion

2019-05-07

Completion

2019-05-07

Countries

• United Kingdom

Study Locations