Pharmacokinetic and Bioequivalence Evaluation of Single‐Tablet and Separate‐Tablet Regimens for Ainuovirine, Lamivudine, and Tenofovir Disoproxil Fumarate in Chinese Healthy Subjects

Abstract This was a single‐dose, randomized, open‐label, 2‐period crossover study to evaluate the bioequivalence of the ACC008 (test formulation [T]) versus coadministered ainuovirine (ANV) 150 mg, lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate 300 mg (reference formulation [R]) in the fasted state among the Chinese healthy adults. Eligible subjects were randomized into 2 cohorts to received treatment in 1 of 2 sequences (T → R, R → T). PK samples were collected from 1 hour before dosing to 144 hours after dosing in each period. The concentrations of ANV, 3TC, and tenofovir in plasma were determined by liquid chromatography–tandem mass spectrometry. Phoenix WinNonlin software was used for pharmacokinetic parameter calculation and bioequivalence evaluation. All the 90% confidence intervals of maximum concentration, area under the concentration–time curve from time zero to the last detectable time, and area under the concentration–time curve from time zero to infinity fell within the bioequivalence range. The safety was comparable between the 2 treatments, with no Grade III/VI or serious adverse events. ACC008 was bioequivalent to administration of its individual components, including ANV 150 mg, 3TC 300 mg, and tenofovir disoproxil fumarate 300 mg with favorable safety profile.