Bioequivalence of a Pediatric Fixed‐Dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Compared With Coadministration of the Separate Agents in Healthy Adults: An Open‐Label, Randomized, Replicate Crossover Study

Abstract

AbstractDarunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a fixed‐dose combination (FDC) for the treatment of HIV‐1 infection in adults and adolescents weighing 40 kg or greater. This Phase 1, randomized, open‐label, 2‐treatment, 2‐sequence, 4‐period replicate crossover study (NCT04661397) evaluated the pivotal bioequivalence of a pediatric D/C/F/TAF 675/150/200/10‐mg FDC compared with coadministration of the separate commercially available formulations in healthy adults under fed conditions. During each period, participants received either a single oral dose of D/C/F/TAF 675/150/200/10‐mg FDC (test) or a single oral dose of darunavir 600 and 75 mg, cobicistat 150 mg, and emtricitabine/tenofovir alafenamide 200/10‐mg FDC (reference). Thirty‐seven participants were randomly assigned to one of 2 treatment sequence groups: test‐reference‐reference‐test or reference‐test‐test‐reference, with 7 days or more washout between periods. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the concentration–time curve from time zero to last measurable concentration, and area under the concentration–time curve extrapolated to infinity for darunavir, cobicistat, emtricitabine, and tenofovir alafenamide fell within conventional bioequivalence limits (80%–125%). No Grade 3/4 adverse events, serious adverse events, or deaths occurred. In conclusion, administration of D/C/F/TAF 675/150/200/10‐mg FDC was bioequivalent to coadministration of the separate commercially available formulations.