From the Instituto de Medicina Molecular (J.J.F.), Faculty of Medicine, University of Lisbon; CNS-Campus Neurológico Sénior (J.J.F.), Torres Vedras, Portugal; University College London (A.J.L.), Reta Lila Weston Institute, UK; Department of Neurology (W.P.), Medical University Innsbruck, Austria; Université de Toulouse (O.R.), CHU de Toulouse, Institut National de la Santé et de la Recherche Médicale, Department of Neurosciences and Clinical Pharmacology, Clinical Investigation Center 1436, and NeuroToul Center of Excellence in Neurodegeneration France; Department of Research and Development (J.-F.R., P.S.-d.-S.), BIAL-Portela & Ca SA, S. Mamede do Coronado, Portugal; Department of Biostatistics (B.K.), Clinipace Worldwide, Eschborn, Germany; and Department of Pharmacology and Therapeutics (P.S.-d.-S.), Faculty of Medicine, University Porto, Portugal.
Neurology. 2018 May 22;90(21):e1849-e1857. doi: 10.1212/WNL.0000000000005557. Epub 2018 Apr 25.
To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease.
After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute "off" time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments.
One year of treatment with opicapone reduced "off" time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in "off" time (-64.9, -39.3, -27.5, and -23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration.
Long-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study.
This study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) of opicapone is well tolerated and reduces "off" time.
评估阿扑卡朋作为左旋多巴辅助治疗的有效性，以及在 1 年的治疗过程中从恩他卡朋转换为阿扑卡朋的效果在伴有波动的帕金森病患者中。
在完成了一项为期 5 周的阿扑卡朋（5、25 或 50mg）安慰剂和恩他卡朋对照双盲研究后，495 例患者继续进入为期 1 年的扩展阶段，在该阶段中患者接受阿扑卡朋治疗。患者开始接受每日 1 次阿扑卡朋 25mg，持续 1 周，随后根据患者的日记进行单独调整左旋多巴和/或阿扑卡朋剂量。主要疗效变量是基于患者日记的绝对“关期”的基线变化。其他结果包括应答者比例、量表评估和标准安全性评估。
与开放标签基线相比，阿扑卡朋治疗 1 年可减少 30 分钟（33.8 分钟）的“关期”，与双盲基线相比可减少 2 小时以上（126.9 分钟）的“关期”。在双盲阶段最初接受阿扑卡朋 50mg 治疗的患者保持了疗效，而转换治疗导致“关期”进一步减少（分别从安慰剂、恩他卡朋和阿扑卡朋 5mg 和 25mg 转换的患者减少 64.9、39.3、27.5 和 23.0 分钟）。异动症是最常报告的不良事件（14.5%），通过调整多巴胺能治疗进行管理。长期使用阿扑卡朋未观察到新的安全性问题。
长期使用阿扑卡朋可在 1 年内提供持续疗效。在研究条件下，从恩他卡朋转换为阿扑卡朋可提高疗效。
这项研究提供了 III 级证据，表明对于患有帕金森病和剂末运动波动的患者，长期使用（52 周）阿扑卡朋耐受良好，并减少“关期”。
