Pharmacokinetic and Bioequivalence Evaluation of Single-Tablet and Separate-Tablet Regimens for Once-Daily Cobicistat-Boosted Elvitegravir in Healthy Japanese Male Subjects: A Randomized, Two-Way Crossover Study

This randomized, two-way crossover study evaluated the bioavailability of elvitegravir administered as the new individual tablet containing 150mg and a cobicistat 150 mg tablet, concomitantly with a fixed-dose combination tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (EVG+COBI+FTC/TDF), in comparison with a single-tablet regimen containing the same dose of each component (EVG/COBI/FTC/TDF). Twenty-four healthy Japanese male subjects received the two different elvitegravir treatments, the separate-tablet or single-tablet regimen, once-daily for 10 days in each. The pharmacokinetic parameters (C-max, AUC(tau), and C-tau) of elvitegravir were investigated at Day 10 after each treatment, together with safety and tolerability. Relative to EVG/COBI/FTC/TDF, the geometric least-squares mean ratios (GMR) and 90% confidence intervals (CIs) for elvitegravir C-max and AUC(tau) were within the boundary of 0.8-1.25, while the upper limit of the 90% CI of GMR for C-tau was narrowly below the lack of bioequivalence boundary (0.79). No deaths, serious AEs, or drug-related AEs occurred. In conclusion, C-max and AUC(tau) of elvitegravir met the strict definition of bioequivalence, indicating that the two regimens were essentially bioequivalent. Treatment with both regimens for 10 days appeared to be safe and well tolerated.