Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study

This study evaluated the effect of a small‐tablet formulation of opicapone for use in clinical trials in Japan on the pharmacokinetics of levodopa (l‐dopa) and 3‐O‐methyldopa (3‐OMD). In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years; body mass index, 18.5 to <30.0 kg/m(2)), 10 mg of l‐dopa/carbidopa 100 was administered 3 times daily on day 0 (period 1) and day 12 (period 3), and opicapone tablets (5, 10, 25, or 50 mg; n = 20 each group) were administered once daily for 11 days (period 2). During periods 1 and 3, plasma concentrations of l‐dopa and 3‐OMD were measured and pharmacokinetic parameters (maximum observed plasma concentration, time at which maximum concentration was observed, area under the plasma concentration–time curve from time 0 to 5 hours [AUC(5h)] and from time 0 to 24 hours [AUC(24h)] following each dose, terminal half‐life) of plasma l‐dopa and 3‐OMD were determined along with the geometric mean ratio (period 3/period 1) of AUC(24h) for l‐dopa and 3‐OMD. Maximum concentration of l‐dopa for the first, second, or third doses of l‐dopa/carbidopa did not significantly increase with increasing opicapone dose. The AUC of l‐dopa increased with increasing opicapone dose but tended toward a peak plateau with opicapone doses of 25 mg and higher. Geometric mean ratios (90% confidence intervals) of AUC(24h) were 5 mg, 1.16 (1.10‐1.21); 10 mg, 1.26 (1.23‐1.30); 25 mg, 1.51 (1.44‐1.57); 50 mg, 1.60 (1.54‐1.66). Opicapone tablets were well tolerated. In Japanese healthy subjects, increases in plasma exposure to l‐dopa appear to level off with opicapone doses of 25 mg and higher, which may be relevant for optimal dosing among Japanese patients with Parkinson disease.