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
Condition: Autoimmune Diseases
MeSH terms: Autoimmune Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    


Intervention name(s): GSK2982772 Modified Release; GSK2982772 Immediate Release
Intervention type(s): Drug; Drug
Intervention description(s): GSK2982772 MR will be available as prototype MR minitablet in capsules with unit dose strength of 60 mg in Part A. In Part B, GSK2982772 MR minitablet in capsules with unit dose strength of 15, 30 or 60 mg will be administered by subjects for Days 1 to 3. In Part C, GSK2982772 MR tablet with unit dose strength of 240, 360 or 480 mg will be administered by subjects. GSK2982772 MR will be administered orally with 240 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 120 mg (4 tablets of dose strength 30 mg) orally with 240 mL of water. In part C, 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 of the study will be a non-randomized 6 period, sequential, 6-way fixed sequence design. Part B of the study will be a repeat dose study. Part C of the study will be a non-randomized 6 period, sequential, fixed sequence crossover design.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: immediate release tablet; GSK2982772; Modified release; minitablet