Bioavailability of the HCV NS3/4A Protease Inhibitor Telaprevir – Effect of Different Types of Food

Aims: Telaprevir (TVR) showed significantly increased SVR rates in Phase 3 studies versus SOC. This study evaluated the impact of different types of food on the bioavailability of orally administered TVR. Methods: In this open-label, randomized, 5-way cross-over trial in 30 HCVnegative, healthy volunteers pharmacokinetic profiles were assessed after single dose administration of TVR 750mg with a regular breakfast (533 kcal, 21g fat), under fasted conditions, with high-fat breakfast (928 kcal, 56g fat), lowcalorie/ high protein breakfast (260 kcal, 9g fat), and low-calorie/low-fat breakfast (249 kcal, 3.6g fat). Subjects fasted for at least 10h prior to drug intake. LSMeans and associated 90% CI of treatment ratios (test/ref) were calculated based on the logtransformed PK parameters to evaluate differences in Cmax and AUC. Regular breakfast was used as reference. Results: Of 30 subjects enrolled, 28 completed the study. Compared to a regular breakfast, TVR exposure (AUC) decreased by 73%, 39% and 26% after administration under fasted conditions, with lowcalorie/ low-fat breakfast, and with low-calorie/high protein breakfast. Administration with high-fat breakfast increased TVR exposure by 20% relative to a regular breakfast. The LSMeans ratio (90% CI) of the TVR AUC and Cmax after intake under fasted conditions was 0.27 (0.22–0.33) and 0.17 (0.13–0.21), after intake with low calorie/low-fat meal 0.61 (0.53–0.69) and 0.62 (0.55–0.71), after intake with low-calorie/high-protein meal 0.74 (0.66–0.83) and 0.75 (0.67–0.83), and after intake with high-fat meal 1.20 (1.03–1.41) and 0.99 (0.87–1.12). Two subjects discontinued (one due to non compliance with the protocol, one due to adverse event). No other grade 3 AEs were reported.Conclusion: TVR should be taken with food to enhance its absorption and optimize exposure. Based on these results recommendation in Phase 3 trials was to take TVR with food/snack that contains some fat. A highfat meal was not required.

Hepatitis C - Pharmakokinetik - Telaprevir