Poster #012:The Relative Bioavailability of Rilpivirine Following Administration of the New Tenofovir Alafenamide Single-tablet Regimen Rilpivirine/Emtricitabine/Tenofovir Alafenamide vs Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate

摘要

Statement of Purpose, Innovation or Hypothesis: Single-tablet regimens (STRs) administered once daily reduce pill burden and are associated with increased adherence, improved virological suppression and patient satisfaction in the treatment of HIV-1 infection. Rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF; ODEFSEY~?) is an STR containing the new tenofovir prodrug tenofovir alafenamide (TAF), which has an improved bone and renal safety profile vs tenofovir disoproxil fumarate (TDF), and was recently approved based on the bioequivalence of TAF and FTC to the elvitegravir/cobicistat/FTC/TAF STR (GENVOYA~?) and the bioequivalence of RPV to RPV single agent (EDURANT~?). This Phase 1 study evaluated the relative bioavailability of RPV following administration of the TAF-based STR RPV/FTC/TAF vs the TDF-containing STR RPV/FTC/TDF (COMPLERA~?; EVIPLERA~?).Description of Methods and Materials: This was a randomized, open-label, two-treatment, two-period, single-center study. Healthy subjects (n = 28) received single doses of RPV/FTC/TAF (25/200/25 mg) and RPV/FTC/TDF (25/200/300 mg) under fed conditions in a crossover manner, separated by a ten-day washout. Intensive pharmacokinetic (PK) sampling was performed and statistical comparisons of RPV exposures were conducted by geometric mean ratios (GMR) and associated 90% CI of 80-125% with RPV/FTC/TAF serving as the test and RPV/FTC/TDF as the reference. Safety was monitored throughout the study and follow-up period. Data and Results: The primary RPV PK parameters (AUC_inf, AUC_last and C_max) and statistical comparisons are presented in Table 1. The PK of RPV was comparable between treatments and the GMR and corresponding 90% CIs of all parameters were contained within the protocol-defined boundary criteria of 80-125%. Both treatments were well tolerated and all subjects completed the study, except one subject who discontinued after the first period due to a Grade 1 adverse event (AE) of raised creatine kinase considered by the investigator as unrelated to the study drug. All AEs observed were mild in severity (Grade 1) and comparable between treatments. Interpretation, Conclusion or Significance: Following administration of RPV/FTC/TAF vs RPV/FTC/TDF, the GMR and corresponding 90% CIs of the primary RPV PK parameters were within the 80-125% boundary of bioequivalence. Administration of RPV/FTC/TAF and RPV/FTC/TDF was well tolerated.