Philipps University, Marburg, Germany.
University of Kansas Medical Center, Kansas City, Kansas, USA.
Mov Disord. 2017 Dec;32(12):1701-1709. doi: 10.1002/mds.27131. Epub 2017 Aug 21.
The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy.
The purpose of this study was to investigate the efficacy and safety of 274 mg ADS-5102 (amantadine) extended-release capsules (equivalent to 340-mg amantadine HCl) for levodopa-induced dyskinesia in a randomized controlled trial.
PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS-5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent-to-treat population. OFF time was a key secondary measure.
At week 12, least-squares mean change in the Unified Dyskinesia Rating Scale was -20.7 (standard error 2.2) for ADS-5102 (n = 37) and -6.3 (standard error 2.1) for placebo (n = 38; treatment difference -14.4, 95% confidence interval -20.4 to -8.3, P < .0001), indicating improvement in levodopa-induced dyskinesia. OFF time decreased 0.5 hours (standard error 0.3) for ADS-5102 from a baseline mean of 2.6 hours and increased 0.6 hours (standard error 0.3) for placebo from a baseline mean of 2.0 hours (treatment difference -1.1 hours, 95% confidence interval -2.0 to -0.2, P = .0199). The most common adverse events (ADS-5102 versus placebo) included dry mouth (13.5% versus 2.6%), nausea (13.5% versus 2.6%), decreased appetite (10.8% versus 0%), insomnia (10.8% versus 0%), orthostatic hypotension (10.8% versus 0%), constipation (8.1% versus 0%), falls (8.1% versus 5.3%), and visual hallucinations (8.1% versus 5.3%). Adverse events led to treatment discontinuation in 19% versus 8%, respectively.
ADS-5102 274 mg is an oral pharmacotherapy demonstrating a significant decrease in levodopa-induced dyskinesia and improving OFF time. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
左旋多巴诱导的帕金森病（PD）运动障碍的治疗是一个未满足的需求，没有批准的药物治疗。
本研究旨在探讨 274mg ADS-5102（金刚烷胺）缓释胶囊（相当于 340mg 盐酸金刚烷胺）治疗左旋多巴诱导的运动障碍的疗效和安全性。
PD 患者有≥1 小时的麻烦性运动障碍，至少有轻度的功能影响，随机分为安慰剂或 ADS-5102 组，每天睡前服用一次，持续 13 周。主要疗效分析是基于改良意向治疗人群中从基线到第 12 周的统一运动障碍评分的变化。OFF 时间是一个关键的次要措施。
在第 12 周，AD5102（n = 37）的统一运动障碍评分的最小二乘均数变化为-20.7（标准误差 2.2），安慰剂（n = 38）为-6.3（标准误差 2.1）（治疗差异-14.4，95%置信区间-20.4 至-8.3，P <.0001），表明左旋多巴诱导的运动障碍得到改善。AD5102 的 OFF 时间从基线平均 2.6 小时减少了 0.5 小时（标准误差 0.3），安慰剂从基线平均 2.0 小时增加了 0.6 小时（标准误差 0.3）（治疗差异-1.1 小时，95%置信区间-2.0 至-0.2，P =.0199）。最常见的不良反应（AD5102 与安慰剂）包括口干（13.5%与 2.6%）、恶心（13.5%与 2.6%）、食欲减退（10.8%与 0%）、失眠（10.8%与 0%）、体位性低血压（10.8%与 0%）、便秘（8.1%与 0%）、跌倒（8.1%与 5.3%）和幻视（8.1%与 5.3%）。不良反应导致治疗中断的比例分别为 19%和 8%。
AD5102 274mg 是一种口服药物治疗，可显著减少左旋多巴诱导的运动障碍，并改善 OFF 时间。
