Pharmacokinetic Comparison of Capsule and Tablet Formulations of Opicapone in Healthy Japanese Subjects: Phase 1 Study

Opicapone, a peripheral, long‐acting catechol‐O‐methyltransferase inhibitor has been shown to improve wearing‐off phenomenon in randomized, double‐blind studies. This study compared the pharmacokinetic characteristics of opicapone small‐tablet and size 1 capsule formulations after single oral administration to healthy Japanese subjects. In this open‐label, randomized, 2‐way and 2‐period crossover phase 1 study, 48 healthy male subjects (aged 20 to 45 years; body mass index, 18.5 to <30.0 kg/m(2)) were randomly assigned to 2 cohorts (n = 24 each), which were administered opicapone 25 or 50 mg in a tablet‐capsule or capsule‐tablet sequence under fasted conditions. Blood samples were collected for pharmacokinetic analysis before opicapone capsule/tablet administration and at regular intervals over 24 hours after administration. Compared with capsules, tablets were associated with higher C(max) and AUC(last/0‐∞) values. However, t(1/2) and t(max) values were similar with opicapone 25‐ and 50‐mg capsules/tablets. Geometric mean ratios (tablets/capsules) of C(max), AUC(last), and AUC(0‐∞) were 1.24, 1.18, and 1.19, respectively, for the 25‐mg dose and 1.42, 1.28, and 1.27, respectively, for the 50‐mg dose. Opicapone was well tolerated, and no serious adverse events occurred. A small tablet formulation of opicapone proposed for use in Japanese clinical trials was associated with apparent greater exposure compared with the existing hard capsule formulation, which should be considered when developing opicapone for Japanese patients.