Pediatric darunavir/cobicistat fixed-dose combination tablet for dispersion: Bioequivalence versus separate agents in healthy participants and acceptability in children living with human immunodeficiency virus-1.

Abstract

ObjectiveThe bioequivalence of the simplified protease-inhibitor-based HIV-1 antiretroviral regimen darunavir/cobicistat (DRV/COBI) 600/90-mg fixed-dose combination (FDC) tablet dispersed in water was evaluated in healthy adults and swallowability in children living with HIV aged >3 years and weighing ≥15 to <25 kg, respectively.MethodsIn the bioequivalence study 32 healthy adult participants received either a single oral dose of the DRV/COBI-600/90-mg FDC tablet dispersed in water (test) or the separate formulations (DRV 100-mg/mL at a dose of 600-mg and COBI 90-mg tablet: reference) separated by ≥ 7 days of washout. In a separate acceptability study children living with HIV-1, aged ≥3 years and weighing ≥15 to <25 kg, received a single oral dose of the dispersed DRV/COBI-600/90-mg FDC tablet. Acceptability questionnaires were completed by observers, participants and caregivers.ResultsThe bioequivalence study indicated that the geometric mean ratios for DRV maximum plasma concentration and area under the concentration-time curve of the dispersed DRV/COBI-600/90-mg FDC tablet versus the separate formulations fell within the 80-125% bioequivalence limits. In the acceptability study in children, per independent observers 83% (10/12) of the children were able to swallow the dispersion completely and rated the dispersed FDC tablet as "ok" to "very easy" to swallow.ConclusionThe DRV/COBI 600/90-mg FDC tablet dispersed in water was bioequivalent to coadministration of the separate formulations and was acceptable for long-term daily use in the intended pediatric population.