Journal of Bioequivalence & Bioavailability

Abstract

Bioequivalence of the Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Single Tablet Regimen

Anita Mathias, M Menning, L Wiser, X Wei, A Dave, S Chuck and BP Kearney

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) is a next-generation, once-daily
complete antiretroviral single-tablet regimen for the treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics and bioequivalence of 2 distinct investigational coformulations of the FTC/RPV/TDF single-tablet regimen (containing emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir disoproxil fumarate 300 mg) compared with the concurrent administration of a 200-mg strength capsule of FTC, a 25-mg strength tablet of RPV, and a 300-mg strength tablet of tenofovir disoproxil fumarate in healthy subjects. Thirty-six subjects were randomized in a single-dose, open-label, 3-way crossover study design; 34 subjects completed all study treatments. Serial blood samples were obtained over 192 hours following oral administration of each treatment and pharmacokinetic parameters calculated. Formulation bioequivalence was assessed by 90% confidence intervals (CI) for the ratio of geometric least square means (GMR) for Cmax, AUClast and AUCinf for each drug of the FTC/RPV/TDF single-tablet regimen versus the individual components. Emtricitabine, rilpivirine, and tenofovir disoproxil fumarate administered under fed conditions (standardized meal of ~400 kcal) as individual drugs given concurrently or as a fixed‑dose combination tablet were generally well tolerated. Of the 2 single-tablet formulations that were tested, a single coformulation (Test Formulation 1) demonstrated bioequivalence to the reference formulation, with 90% confidence intervals for the ratio of the geometric least-squares means contained within the bounds of 80% to 125% for the AUCinf, AUC0−last, and Cmax values of emtricitabine, rilpivirine, and tenofovir, and was carried forward as the commercial formulation. This tablet is a next-generation, once-daily single-tablet antiretroviral regimen for the treatment of HIV-1
infection and offers an attractive treatment option to efavirenz-containing regimens.