Bioequivalence of a Fixed-Dose Combination Tablet of the Complete 2-Drug Regimen Dolutegravir and Rilpivirine for the Treatment of HIV-1 Infection [PublishAheadOfPrint]

Background: A complete 2-drug regimen of dolutegravir 50 mg and rilpivirine 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability. This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with separate tablets. Secondary endpoints were tolerability and safety of the fixed-dose combination tablet.

Methods: In this open-label, randomized-sequence, 2-way crossover trial, single doses of the fixed-dose combination tablet (test) and the combination of separate tablets (reference) were administered to healthy adults after a moderate-fat meal, with a 21-day washout between treatments. Pharmacokinetic samples were collected through 12 days after dosing. The primary endpoints were area under the plasma concentration-time curve (AUC) and maximum concentration of drug (C_max). The study employed a prespecified sample-size re-estimation based on a blinded midpoint review of C_max variability to update the enrollment size to achieve statistical power.

Results: Of 118 participants enrolled, 113 received both treatments and underwent pharmacokinetic assessment. The 90% confidence intervals for the geometric least squares means ratios for AUC_0-, AUC_0-t, and C_max (test vs reference) were within the bioequivalence range of 0.80 to 1.25 for both drugs, indicating bioequivalence. In this study, a single dose of either treatment was well tolerated overall, with 4% (n=5) and 3% (n=3) of participants reporting adverse events considered related to the test and reference treatments, respectively.

Conclusions: The dolutegravir/rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets and no new safety signals emerged.

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