A study evaluating the pharmacokinetics, safety, and tolerability of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) single tablet regimen (STR) in Japanese subjects
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]
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.
H. Zhang1, S. West2, A. Vu3, R. Humeniuk1, D. Xiao4, H. Graham5, H. Martin5, J. Custodio1
1Gilead Sciences, Clinical Pharmacology, Foster City, United States, 2Gilead Sciences, Biometrics, Foster City, United States, 3Gilead Sciences, Clinical Operations, Foster City, United States, 4Gilead Sciences, Bioanalytical Chemistry, Foster City, United States, 5Gilead Sciences, Clinical Research, Foster City, United States