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Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study
Author(s) -
Nomoto Masahiro,
Takeda Atsushi,
Iwai Katsuaki,
Nishimura Akihisa,
Hattori Nobutaka
Publication year - 2021
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.799
Subject(s) - medicine , pharmacokinetics , carbidopa , confidence interval , crossover study , half life , levodopa , pharmacology , parkinson's disease , alternative medicine , disease , pathology , placebo
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.