Background: Bictegravir (BIC) is an investigational, once-daily, unboosted HIV integrase strand transfer inhibitor (INSTI) with a high barrier to resistance and potent in vitro activity against most INSTI-resistant variants. BIC, coformulated with the NRTI backbone of emtricitabine/tenofovir alafenamide (FTC/TAF), is currently in development for treatment of HIV-1 infection. This study evaluated the pharmacokinetics (PK), safety, and tolerability of BIC/FTC/TAF (B/F/TAF) in HIV-uninfected Japanese and Caucasian subjects.
Methods: Japanese subjects (n=25) were born in Japan, had not lived outside Japan > 5 years, and had traceable maternal and paternal Japanese ancestry of parents and grandparents. Caucasian subjects (n=25) were not of Japanese or Asian descent. All subjects received a single, oral dose of B/F/TAF (50/200/25 mg) under fasted conditions. Intensive PK sampling was performed and statistical comparisons of the exposures of BIC, FTC, TAF, and TAF metabolite, TFV, were conducted by geometric mean ratios (GMR), associated 90% confidence intervals (CI), and no-effect boundary of 70-143%, with Japanese subjects as the test and Caucasian subjects as the reference. Safety was monitored throughout the study and follow-up.
Results: Table 1 shows the primary BIC, FTC, TAF, and TFV PK parameters (AUCinf, AUClast, Cmax) and statistical comparisons. The PK of all components of B/F/TAF was similar in Japanese and Caucasian subjects and the GMR and corresponding 90% CIs of all parameters were contained within the protocol-defined no-effect boundary of 70%-143%. B/F/TAF was well tolerated and all subjects completed the study except one Caucasian subject who discontinued due to adverse events (AEs) of Grade 2 nausea and Grade 1 vomiting. No Grade 3, 4, or serious AEs and no clinically relevant laboratory abnormalities were observed.

B/F/TAF PK Parameter Summary
[B/F/TAF PK Parameter Summary]

Conclusions: Following administration of B/F/TAF, equivalent pharmacokinetics and similar safety and tolerability were observed in Japanese and Caucasians subjects supporting the use of the 50/200/25 mg dose of B/F/TAF in HIV-infected Japanese patients.