Faldaprevir (FDV) is a novel NS3/NS4A inhibitor used in the treatment of hepatitis C infection in an interferon-free regimen. This study evaluated the safety, tolerability, and pharmacokinetics of FDV following a single dose in healthy male subjects and assessed the effect of food on FDV bioavailability. In the placebo-controlled, randomized, single-blind, single-increasing-dose part of the study (Part 1), 64 healthy male subjects were randomized to receive FDV in PEG/ TRIS/meglumine solution at one of eight dose levels (4–1,200 mg, n = 6 per dose group) or placebo (n = 2 per dose group). In Part 2, the effect of food on the relative bioavailability (rBA) of 480 mg FDV in solution was evaluated in an openlabel, crossover comparison, with and without a high-fat breakfast, in an additional 10 subjects (8 FDV and 2 placebo). Following single doses of 4–1,200 mg FDV, geometric mean (gMean) Cmax and AUC0-inf were 3.57–16500 ng/mL and 254–402000 h*ng/mL, respectively, displaying more than dose-proportional increases in exposure. FDV was slowly absorbed, with gMean t1/2 and median tmax of 15.5–39.2 h and 4.0–14.0 h, respectively; both were dose dependent. The urinary excretion of FDV was less than 0.1% of the dose. A high-fat breakfast increased systemic exposure to FDV in solution by 14%. FDV was generally well tolerated; subjects who experienced adverse events (AEs) recovered without sequelae, and no serious AEs were reported. Indirect (unconjugated) bilirubin of >3.0 mg/dL was observed in two subjects at 480 mg and five subjects at 1,200 mg. In conclusion, at single doses of 4–1,200 mg in healthy male subjects, FDV showed dose-dependent pharmacokinetics and was generally considered safe and well tolerated. Food had no clinically relevant effect on the rBA of FDV.
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