Ferreira Joaquim J, Poewe Werner, Rascol Olivier, Stocchi Fabrizio, Antonini Angelo, Moreira Joana, Pereira Ana, Rocha José-Francisco, Soares-da-Silva Patrício
Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Neurol Ther. 2022 Sep;11(3):1409-1425. doi: 10.1007/s40120-022-00371-7. Epub 2022 Jun 16.
Levodopa remains the cornerstone treatment for Parkinson's disease (PD) but its use is associated with the development of 'wearing-off' fluctuations and other motor and non-motor complications over time. Adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/dopa decarboxylase (DDC) inhibitor therapy reduces fluctuations in the profile of plasma levodopa levels following oral dosing, and can therefore be beneficial for the management of motor complications. The objective of the EPSILON study is to investigate the efficacy of opicapone (OPC; a third-generation, once-daily COMT inhibitor) in enhancing the clinical benefit of levodopa in patients in earlier stages of PD, without end-of-dose motor fluctuations.
EPSILON is a phase III, double-blind, randomised, placebo-controlled and parallel-group study, designed to evaluate the efficacy and safety of OPC as add-on to levodopa/DDC inhibitor therapy in patients with early PD who do not exhibit signs of motor complications. Eligible patients will be randomised (1:1) to receive OPC 50 mg or placebo, in addition to their existing levodopa/DDC inhibitor therapy, over a 24-week, double-blind treatment period, after which they will have the option of entering an additional 1-year, open-label extension period, during which all patients will receive OPC 50 mg.
The primary efficacy endpoints are change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III total score from baseline to the end of the double-blind period (double-blind phase) and change in MDS-UPDRS Part IV total score from open-label baseline to the end of the open-label period (open-label phase). Secondary outcomes during the double-blind phase will include other measures of PD symptoms, including quality of life, non-motor symptoms, and development of motor fluctuations. Safety assessments will include evaluation of treatment-emergent adverse events, laboratory safety parameters, suicidality and impulse control disorders.
European Union Drug Regulating Authorities Clinical Trials Database (number 2020-005011-52).
左旋多巴仍然是帕金森病（PD）的基石治疗药物，但随着时间的推移，其使用与“剂末”波动以及其他运动和非运动并发症的发生有关。在左旋多巴/多巴脱羧酶（DDC）抑制剂治疗中添加儿茶酚-O-甲基转移酶（COMT）抑制剂可减少口服给药后血浆左旋多巴水平曲线的波动，因此对运动并发症的管理可能有益。EPSILON研究的目的是调查opicapone（OPC；一种第三代每日一次的COMT抑制剂）在增强早期PD患者左旋多巴临床获益方面的疗效，这些患者无剂末运动波动。
EPSILON是一项III期、双盲、随机、安慰剂对照的平行组研究，旨在评估OPC作为左旋多巴/DDC抑制剂治疗的附加药物，在未出现运动并发症迹象的早期PD患者中的疗效和安全性。符合条件的患者将被随机分配（1:1）接受50mg OPC或安慰剂，在现有的左旋多巴/DDC抑制剂治疗基础上，进行为期24周的双盲治疗期，之后他们可以选择进入为期1年的开放标签延长期，在此期间所有患者将接受50mg OPC。
主要疗效终点是从基线到双盲期结束（双盲阶段）运动障碍协会统一帕金森病评定量表（MDS-UPDRS）第三部分总分的变化，以及从开放标签基线到开放标签期结束（开放标签阶段）MDS-UPDRS第四部分总分的变化。双盲阶段的次要结果将包括其他PD症状指标，包括生活质量、非运动症状和运动波动的发生情况。安全性评估将包括对治疗中出现的不良事件、实验室安全参数、自杀倾向和冲动控制障碍的评估。
欧盟药品监管当局临床试验数据库（编号2020-005011-52）。
