This study will evaluate two new GSK1265744 sodium salt tablet formulations and provide data for selection of one of these tablet formulations for use in Phase 3. This is a single-center, randomized, two part, open-label, crossover study in healthy adult subjects. Part A is a randomized, open-label, 3-way balanced cross-over design in 24 subjects to assess the oral bioavailability of two GSK1265744 sodium salt tablet formulations relative to the current GSK1265744 sodium salt formulation being used in the phase IIb studies under fasting conditions. Part A treatment periods will be separated by a 14 day washout. After completion of Part A, preliminary PK data will be analyzed and a decision will be made based on pre-specified criteria, as to which formulation will be used to conduct Part B. Fifteen subjects who will have participated in Part A will participate in Part B and receive the selected formulation with a moderate fat meal. All treatments will be administered as single 30 mg doses of GSK1265744. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 10 - 14 days after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
GSK1265744 (micronized) reference formulation is available as 30 mg tablet to be orally administered with 240 mL of water
GSK1265744 (micronized) New formulation 1 is available as 30 mg tablet to be orally administered with 240 mL of water
GSK1265744 (un-micronized) New formulation 2 is available as 30 mg tablet to be orally administered with 240 mL of water
GSK Investigational Site
Overland Park, Kansas, United States
Part A: Composite of pharmacokinetic (PK) parameters to evaluate the relative bioavailability of GSK1265744 in the fasted state
PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-infinity\]), AUC from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]), maximum observed concentration (Cmax) and concentration at 24h post-dose (C24)
Time frame: Pre-dose, 0.5 hour(hr), 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose
Part B: Composite of PK parameters to evaluate the relative bioavailability of GSK1265744 in the fed state
PK parameters will include AUC(0-infinity), AUC(0-t), Cmax and C24
Time frame: Pre-dose, 0.5 hr, 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose
Part A: Composite of other PK parameters following administration of GSK1265744 in the fasted state
Other PK parameters will include apparent terminal phase half-life (t1/2), absorption lag time (tlag), time to Cmax (tmax), the percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), time of last measurable concentration (tlast) and apparent oral clearance (CL/F)
Time frame: Pre-dose, 0.5hr, 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose
Part A: Safety and tolerability parameters, including adverse events, concurrent medication, clinical laboratory screens, ECG, and vital signs assessments
Clinical laboratory screens will include haematology, clinical chemistry and urinalysis. Vital sign assessment will include systolic and diastolic blood pressure and heart rate
Time frame: Up to 13 weeks
Part B: Composite of other PK parameters following administration of GSK1265744 in the fed state
Other PK parameters will include t1/2, tlag, tmax, %AUCex, tlast and CL/F
Time frame: Pre-dose, 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose
Part B: Safety and tolerability parameters will include adverse events, concurrent medication, clinical laboratory screens, ECG, and vital signs assessments
Clinical laboratory screens will include haematology, clinical chemistry and urinalysis
Time frame: Up to 18 weeks
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