Effect of food on the pharmacokinetics of emtricitabine/rilpivirine/tenofovir disoproxil fumarate single‐tablet regimen

Abstract

Purpose

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF; Complera®/Eviplera®) is a recently approved complete single tablet regimen (STR) for treatment‐naïve HIV‐1‐infected patients. Exposures of rilpivirine single agent Edurant®) are 40% lower when administered under fasted conditions versus standard meal (533 kcal) or high‐fat/high caloric meal (928 kcal). The present study evaluated the effect of standard and light meal on FTC/RPV/TDF pharmacokinetics (PK).

Methods

This was a three‐period, six‐sequence, crossover single‐dose study (N = 24) in healthy subjects that received FTC/RPV/TDF with a standard meal (540 kcal, 21 g fat), light meal (390 kcal, 12 g fat) or under fasted conditions (each treatment 18 days apart). Blood sampling was done for 192 hrs and PK of RPV, FTC, and tenofovir (TFV) were evaluated. Safety was monitored throughout the study and at 14‐day follow‐up. Exposures of study drugs from the various treatments were compared to fasted or standard meal as reference using 90% confidence interval (CI) bounds of 80 to 125% about the geometric mean ratio (GMR).

Results

Of the 24 enrolled subjects, 23 completed. There were no Grade 3 or 4 adverse events (AEs), serious AEs, or AEs leading to discontinuation. Compared to fasting conditions, RPV AUC_inf was 9% and 16% higher with a light meal or standard meal, respectively. Compared to standard meal, RPV AUC_inf was 14% and 6% lower with fasted or light meal administration, respectively. TFV and FTC exposures were consistent with their established PK/food effect (Table 1).

Conclusion

Administration with food has a modest effect on RPV PK as FTC/RPV/TDF STR versus fasted dosing, with no relevant differences between a light meal versus standard meal. FTC/RPV/TDF STR can be administered with a light or standard meal.