Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations. This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of a 50 mg granule formulation of dolutegravir when administered 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula compared to the current 50 mg tablet formulation administered with tap water. Safety evaluations and serial PK samples will be collected during each treatment period. A taste assessment of the granule will also be performed. A follow-up visit will occur 5-7 days after the last dose of study drug. Pharmacokinetic assessments during the study will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t)), maximum observed concentration (Cmax), terminal phase half-life (t½), lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), concentration at 24 hours post-dose (C24), and apparent clearance following oral dosing (CL/F).
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
20
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
GSK Investigational Site
Austin, Texas, United States
Plasma DTG AUC(0-infinity), AUC(0-t), and Cmax
Time frame: 48 hours post dose
Plasma DTG t½, tlag, tmax, C24, and CL/F
Time frame: 48 hours post dose
Safety and tolerability parameters as assessed by change from baseline in 12-lead ECG and vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests
Time frame: 6 weeks
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