Evaluation of the Bioequivalence of a Combined Formulated Tablet
Status:
Completed
Trial end date:
2012-08-01
Target enrollment:
Participant gender:
Summary
Dolutegravir (DTG, GSK1349572) is a next-generation integrase inhibitor (INI) currently in
phase 3 clinical trials for human immunodeficiency virus (HIV). Fixed-dose combinations
(FDCs) have greatly simplified the treatment of patients with HIV. While Atripla (an FDC of
tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) has become the preferred first line
regimen due in large part to its convenient presentation as a full treatment regimen in a
single product, other options are needed. A fixed-dose combination of DTG/abacavir
(ABC)/lamivudine (3TC) is one such opportunity. Part A of this study will be a single-dose,
two-treatment crossover pivotal bioequivalence (BE) evaluation of the DTG/ABC/3TC FDC tablet
in 66 healthy subjects. The reference formulations in this trial will be the 50 mg DTG tablet
that is currently being used in the Phase 3 clinical trials and the already marketed FDC
tablet product EPZICOM™ (ABC 600 mg/3TC 300 mg).It is intended that the results of this
pivotal bioequivalence study will show that the proposed commercial DTG/ABC/3TC FDC tablet
formulation is bioequivalent to DTG plus EPZICOM administered as separate tablets. Part B of
this study will evaluate the effect of a high fat meal on the FDC tablet in 12 healthy
subjects that have already participated in Part A of the study. There will be a screening
visit within 30 days prior to the first dose of study drug and a follow up visit within 7-14
days after the last dose. There will be a 7 day washout between doses in each treatment
period. The following PK parameters for DTG, ABC and 3TC will be measured: area under the
concentration 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 the
time of the last quantifiable concentration (AUC (0-t)), maximum observed concentration
(Cmax), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax
(tmax), terminal phase half-life (t½), terminal elimination phase rate constant (λz),
percentage of AUC obtained by extrapolation (%AUCex),apparent clearance following oral dosing
(CL/F) and apparent terminal phase volume