Bioequivalence of the co-formulation of emtricitabine/rilpivirine/tenofovir DF
A. Mathias, M. Menning, X. Wei, A. Dave, S. Chuck, B.P. Kearney
Gilead Sciences, Foster City, United States
Background: Rilpivirine (RPV, TMC278) 25mg QD has demonstrated efficacy similar to efavirenz with an improved safety profile with respect to CNS AEs, lipid abnormalities, incidence of rash in Phase 2 studies and is not teratogenic. RPV is currently under evaluation in Phase 3 clinical trials in treatment-naïve HIV-1 patients in combination with the DHHS- and EACS-preferred NRTI backbone agents emtricitabine (FTC 200mg) and tenofovir disoproxil fumarate (TDF 300mg). This study evaluated the bioequivalence of a FTC/RPV/TDF fixed dose regimen tablet (FDR) to coadministration of the individual components (FTC+RPV+TDF).
Methods: A randomized, single-dose, open-label, Phase 1 study in healthy adults under fed conditions. Serial blood samples were obtained over 192 hours following oral administration of each treatment and PK 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 FDR versus the individual components.
Results: 36 subjects enrolled and 34 completed the study. All treatments were generally well tolerated; most adverse events were mild in severity. PK parameters are presented below; all PK parameters met the criteria for bioequivalence.
[Mean (CV%) PK Parameter]
Cmax: ng/mL, AUC: ng*hr/mL
Conclusions: The FTC/RPV/TDF fixed dose regimen tablet is bioequivalent to its individual components. This tablet is a next-generation, once-daily single-tablet antiretroviral regimen for the treatment of HIV‑1 infection and may offer an attractive alternative to efavirenz-containing regimens due to tolerability concerns and potential reproductive risks.
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