National Hospital Organization, Sendai-Nishitaga Hospital, 2-11-11 Kagitorihoncho, Taihaku-ku, Sendai, 982-8555, Japan.
Department of Cognitive and Motor Aging, Tohoku University, Graduate School of Medicine, Sendai, Japan.
J Neural Transm (Vienna). 2021 Mar;128(3):337-344. doi: 10.1007/s00702-021-02315-1. Epub 2021 Feb 25.
The double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson's Disease) study in Japanese levodopa-treated patients with Parkinson's disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [- 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [- 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [- 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.
COMFORT-PD（COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson's Disease）研究的双盲部分纳入了日本左旋多巴治疗的帕金森病伴运动波动患者，结果显示，opicapone 25mg 和 50mg 均明显优于安慰剂。这项为期 52 周的开放标签延伸研究评估了 opicapone 50mg 片剂在完成 COMFORT-PD 研究双盲部分的患者中的长期安全性和疗效。安全性通过不良事件、实验室检查以及身体、心血管和神经检查进行监测。疗效主要通过停机时间的变化来评估。次要疗效指标包括：双盲部分的 ON 时间、OFF/ON 时间应答者的百分比、其他结果。391/437 名患者转入开放标签延伸期，并纳入安全性分析集（全分析集，n=387；开放标签完成者，n=316）。不良事件频繁报告（n=338，86.4%），但<50%被认为与药物相关（39.9%），很少被认为严重（2.6%）或导致停药（2.8%）。在开放标签期内，无论初始随机分组如何，停机时间均持续减少。从开放标签基线到最后一次就诊的停机时间变化[LSM（SE）]显示，初始随机分配至 opicapone 25mg 组的患者[-0.37（0.20）h，P=0.0689]和 opicapone 50mg 组[-0.07（0.21）h，P=0.6913]持续有效，而 opicapone 50mg 导致先前安慰剂组显著减少[-1.26（0.19）h，P<0.05]。每日一次的opicapone 50mg 通常具有良好的耐受性，在 52 周内持续减少日本左旋多巴治疗的伴运动波动的帕金森病患者的停机时间。
试验注册 JapicCTI-153112；注册日期：2015 年 12 月 25 日。
