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This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50\u00a0mg 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, <jats:italic>n<\/jats:italic>\u2009=\u2009387; open-label completers, <jats:italic>n<\/jats:italic>\u2009=\u2009316). Adverse events were frequently reported (<jats:italic>n<\/jats:italic>\u2009=\u2009338, 86.4%), but\u2009&lt;\u200950% 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\u00a0mg [\u2212\u00a00.37 (0.20) h, <jats:italic>P<\/jats:italic>\u2009=\u20090.0689] and opicapone 50\u00a0mg [\u2212\u00a00.07 (0.21) h, <jats:italic>P<\/jats:italic>\u2009=\u20090.6913] whereas opicapone 50\u00a0mg led to a statistically significant reduction in the previous placebo group [\u2212\u00a01.26 (0.19) h, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05]. Once-daily opicapone 50\u00a0mg was generally well tolerated and consistently reduced OFF-time over 52\u00a0weeks in Japanese levodopa-treated patients with motor fluctuations.<\/jats:p><jats:p><jats:italic>Trial registration<\/jats:italic> JapicCTI-153112; date of registration: December 25, 2015.<\/jats:p>","DOI":"10.1007\/s00702-021-02315-1","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T10:03:39Z","timestamp":1614247419000},"page":"337-344","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Long-term safety and efficacy of opicapone in Japanese Parkinson\u2019s patients with motor fluctuations"],"prefix":"10.1007","volume":"128","author":[{"given":"Atsushi","family":"Takeda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nomoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihisa","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"2315_CR1","doi-asserted-by":"publisher","first-page":"S39","DOI":"10.1212\/wnl.62.1_suppl_1.s39","volume":"62","author":"DJ Brooks","year":"2004","unstructured":"Brooks DJ (2004) Safety and tolerability of COMT inhibitors. 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Inc., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd. and Kyowa Kirin Co., Ltd., and personal fees from Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd. and Abbvie Inc. RT received grants from Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Eisai Co., Ltd., Sanofi K.K., Pfizer Japan Inc., Novartis Pharma K.K., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nihon Medi-Physics Co., Ltd., Japan Blood Products Organization and Medtronic Japan Co., Ltd. and personal fee from KAN Research Institute, Inc., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd. and FP Pharmaceutical Corporation. YT received grants from Ono Pharmaceutical Co., Ltd. MN received grants from Ono Pharmaceutical Co., Ltd, and personal fees from Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Hisamitsu Pharmaceutical Co. Inc., Meiji Seika Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd. and Kissei Pharmaceutical Co., Ltd. TM received other funding from Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., FP Pharmaceutical Corporation, Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Abbvie Inc. and Nippon Boehringer Ingelheim Co., Ltd. NH received grants and other funding from Ono Pharmaceutical Co., Ltd., grants from Japan Agency for Medical Research and Development (AMED), Japan Society for the Promotion of Science (JSPS) and Ministry of Education Culture, Sports, Science and Technology Japan (Grant-in-Aid for Scientific Research on Innovative Areas), personal fees from International Parkinson and Movement Disorder Society, Acorda Therapeutics, Inc., Sanofi K.K., Pfizer Japan Inc., Alexion Pharmaceuticals, Inc., Mylan N.V., MSD K.K. and Lundbeck Japan K.K., personal fees and other from Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd., FP Pharmaceutical Corporation, Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Nihon Medi-physics Co., Ltd., Novartis Pharma K.K., Biogen Inc., Abbvie Inc., Astellas Pharma Inc. and Daiichi Sankyo Co., Ltd., non-financial supports from IBM Japan, Ltd., non-financial supports and other from Boston Scientific Japan K.K. and others from Medtronic, Inc., Mitsubishi Tanabe Pharma Corporation, Hydrogen Health Medical Labo Co., Ltd., ABIST Co., Ltd., Melodian Co., Ltd., Daiwa Co., Ltd., Bayer Yakuhin, Ltd., Nihon Pharmaceutical Co., Ltd., Asahi Kasei Medical Co., Ltd., MiZ Co., Ltd., OHARA Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd. and Hisamitsu Pharmaceutical Co., Inc. KY and AN are employees of Ono Pharmaceutical Co., Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by institutional review boards at each of the participating institutions. This study was conducted in compliance with the spirit of the Declaration of Helsinki and the \u201cAct on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics\u201d and \u201cGuideline for Good Clinical Practice\u201d (International Conference on Harmonisation [ICH] E6 Guideline) as well as \u201cMinisterial Ordinance Concerning Good Clinical Practice (GCP)\u201d (Japanese Ministry of Health and Welfare Ordinance No. 28 and related amendments) and its related notifications.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients provided written informed consent before participation in the double-blind period of the study, which was designed such that only patients who completed the double-period were transferred to the open-label period.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}