Sixteen healthy subjects will be randomized to each of the 3 parallel treatment groups. Eligible subjects will check in to the clinical unit on Day -2 and have 24-hr pharmacokinetic collections on Day -1 and on Day 1. Once the pharmacokinetic parameters of the formulations have been analyzed, doses of GSK2212836 will be selected for further study in Part B. Subjects from Part A will participate in Part B. Part B is a single blind, randomized, placebo controlled study that will consist of a 2-week repeat dose period with 3 dose levels and one dose of the marketed formulation of GSK2212836. Subjects will check in to the clinical unit on Day -3; will participate in a test meal on Day -2 and have 24-hr baseline pharmacokinetic profiles on Day -1 and Day 1. Subjects will be released from the clinic on Day 2, and return for daily dosing on Days 3 through 12. On Day 6, they will also have a brief outpatient visit. Subjects will check into the clinic again on the evening of Day 12, and on Day 13 they will again have 24-hr pharmacokinetic profiles collected. Subjects will be released from the clinical research unit on Day 14, following a test meal, triglyceride sampling and check-out assessments, and will be released from the study 5-10 days later after completing a follow up visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
46
Treatment A - GSK2212836 test formulation 1, Treatment B - GSK2212836 test formulation 2, or Treatment C -GSK2212836 marketed formulation.
Treatment D - low dose of GSK2212836 test formulation, Treatment E - medium dose of GSK2212836 test formulation, Treatment F - high dose of GSK2212836 test formulation, Treatment G - GSK2212836 marketed formulation, or Placebo.
GSK Investigational Site
Buffalo, New York, United States
Part A: To determine the total (AUC(0 to infinity)) and peak (Cmax) exposure of GSK2212836
Time frame: 24 hours
Part B: PK parameters AUC(0-24h) and Cmax following 14 days of dosing with GSK2212836
Time frame: 14 days
Part A: To assess the relative bioavailability of GSK2212836 test capsules vs the reference formulation GSK2213836
Time frame: 24 hours
Part B: To estimate the accumulation and dose proportionality of GSK2212836 after repeat dosing of the test formulation
Time frame: 14 days
Part A: Safety and tolerability parameters following single doses of GSK2212836 test formulation including adverse events, clinical laboratory, ECGs and vital signs assessments.
Time frame: 24 hours
Part A: Secondary PK parameters including: tmax, t1/2 and baseline-corrected AUC(0-24h)
Time frame: 24 hours
Part B: Safety and tolerability parameters following repeat doses of GSK2212836 test formulation including adverse events, clinical laboratory, ECGs and vital signs assessments
Time frame: 14 days
Part B: Secondary PK parameters including: tmax, t1/2
Time frame: 14 days
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