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

Darunavir/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.

Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1–infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study

“…[8][9][10][11] Bioequivalence of D/C/F/TAF FDC relative to combined administration of the separate commercially available agents has been demonstrated in both adult and pediatric populations. [12][13][14] As such, D/C/F/TAF is approved at doses of 800/150/200/10 mg in several countries for the treatment of HIV-1 infection in adults and adolescents weighing ≥40 kg 15,16 and is under development as a scored D/C/F/TAF 675/150/200/10 mg tablet containing 675 mg of darunavir (as ethanolate), 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide (as fumarate) for pediatric patients ≥6 to <18 years who weigh ≥25 to <40 kg.…”