A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772
Condition: Autoimmune Diseases
MeSH terms: Autoimmune Diseases
Study type: Interventional
Phase: Phase 1

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).
    


Intervention name(s): GSK2982772 Modified Release; GSK2982772 Immediate Release
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Part A will be a 6-period, 6-way fixed sequence design, in which up to 4 MR tablet prototype coated formulation will be evaluated, following single dose administration (240 mg) in fasted or fed state. There will be a minimum 7-day washout between doses. Part B of the study is optional. Following the final period of Part A, there will be an interim review to determine whether to proceed with optional Part B, and if so, the formulations and tablet strengths to be investigated in Part B. 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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tablet formulation; Sequence; Immediate release; Pharmacokinetic