Randomized, Controlled Study of Opicapone in Japanese Parkinson's Patients with Motor Fluctuations

Abstract

Objectives This placebo‐controlled, randomized study evaluated the efficacy and safety of opicapone 25‐mg and 50‐mg tablets in Japanese levodopa‐treated patients with Parkinson's disease and motor fluctuations. Methods Japanese adults (n = 437, age 39–83 years) with Parkinson's disease (United Kingdom Parkinson's Disease Society criteria) received opicapone 25‐mg (n = 145), opicapone 50‐mg (n = 145), or placebo (n = 147) tablets over the double‐blind treatment period (14–15 weeks). The primary efficacy assessment was change in OFF‐time; secondary efficacy assessments included OFF/ON‐time responders (≥1 hour change from baseline), total ON‐time, ON‐time with and without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale. Results The least squares mean (standard error) change in OFF‐time from baseline to the last visit was −0.42 (0.21) hour for the placebo group, −1.16 (0.22) hour for the opicapone 25 mg group, and −1.04 (0.21) hour for the opicapone 50 mg group. The percentage of ON‐time responders, changes in total ON‐time/ON‐time without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale II (at OFF) all showed statistically significant improvements versus placebo for both opicapone tablet doses (P < 0.05). Unified Parkinson's Disease Rating Scale III (at ON) was improved versus placebo in patients who received opicapone 50 mg (P < 0.05). Adverse events were more common in patients treated with opicapone 25 mg (60.0%) or opicapone 50 mg (54.5%) versus placebo (48.3%). The most commonly reported adverse event was dyskinesia (placebo, 2.7%; opicapone 25 mg, 9.0%; opicapone 50 mg, 12.4%). Conclusions In Japanese patients, both opicapone 25 and 50 mg were significantly more effective than placebo with no dose‐dependent difference in efficacy, and both doses were well tolerated. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical Utility of Opicapone in the Management of Parkinson’s Disease: A Short Review on Emerging Data and Place in Therapy

“… 40 Overall, the efficacy results in this study are broadly consistent with those seen in BIPARK I and II, however the least squares mean changes in OFF-time were numerically lower in Japanese patients than in the BIPARK I and II studies for OPC 25 mg, 50 mg, and placebo. 26 , 40 …”

“… 40 The main conclusion of this study is that once-daily adjunct OPC tablets at doses of 25 and 50 mg significantly reduced OFF-time compared with placebo among Japanese L-Dopa treated patients with PD and motor fluctuations, with no dose dependency between OPC tablet dosages. 40 Overall, the efficacy results in this study are broadly consistent with those seen in BIPARK I and II, however the least squares mean changes in OFF-time were numerically lower in Japanese patients than in the BIPARK I and II studies for OPC 25 mg, 50 mg, and placebo. 26 , 40 …”

“… 39 OPC tablets were further studied in Japanese PD patients with motor fluctuations in a randomized placebo-controlled study, the double-blind part of COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease). 40 The study design was similar to BIPARK I and II clinical trials. Recruited Japanese PD patients had lower OFF-time and used lower L-Dopa doses.…”

Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone

“…The efficacy of adjunct opicapone in reducing OFF time in patients with motor fluctuations has been well established in phase 3 clinical trials, as well as in observational studies, and has been extensively reviewed elsewhere [73][74][75]. Three randomized, double-blind, placebo-controlled studies have examined the symptomatic effects of opicapone in PD patients with motor fluctuations, namely the BIPARK studies (I and II) [76,77] and, more recently, a phase 2b (COMFORT-PD) study conducted in the Japanese population [78]. Key findings from the separate studies are given in Table 1.…”

Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations

“…Although previous studies have confirmed that the pharmacokinetic and pharmacodynamic profiles of opicapone are similar in Japanese and non-Japanese populations (Falcao et al 2016), there has been a lack of studies on the clinical efficacy and safety of opicapone in Japanese patients. Prior to this study, we conducted a double-blind, randomized, placebo-controlled study with opicapone tablets developed by Ono Pharmaceutical Co. Ltd. (Osaka, Japan) to evaluate the efficacy and safety of opicapone 25 mg and 50 mg tablets versus placebo in Japanese patients with PD and motor fluctuations despite treatment with an L-dopa and DCI combination (Takeda et al 2021). Results of this double-blind study found that, compared with placebo, both opicapone 25 mg and 50 mg tablets were associated with statistically significant reductions in OFF-time as well as improvements in other endpoints, including the percentage of ON-time responders and changes in total ON-time/ONtime without troublesome dyskinesia.…”