Department of Neurology, Parkinsons Disease and Movement Disorders Program, Center for Neurological Health, College of Medicine, University of Toledo, 3000 Arlington Avenue, MS 1195, Toledo, OH 43614 2598, USA.
Parkinsonism Relat Disord. 2012 Jun;18(5):488-93. doi: 10.1016/j.parkreldis.2012.01.008. Epub 2012 Feb 10.
This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD).
Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score.
Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment.
This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients.
本研究为 6 个月双盲、随机研究的前瞻性开放标签扩展研究（SP702；NCT00594165），旨在评估罗替高汀透皮系统治疗早期帕金森病（PD）的长期安全性和耐受性。
早期特发性 PD 患者接受罗替高汀透皮治疗，最长达 6 年，剂量最佳（最高 16mg/24h），可联合使用左旋多巴。主要结局包括不良事件（AE）和罗替高汀暴露程度。其他结局包括左旋多巴起始时间、异动症发生率以及使用统一帕金森病评定量表（UPDRS）Ⅱ+Ⅲ总分评估的疗效。
217 例入组双盲研究的患者中，47%在研究结束时仍在接受开放标签治疗；24%因 AE 停药，6%因疗效不佳停药。罗替高汀暴露的中位时间为 1910 天（≈5 年 3 个月；范围 1-2188 天）。最常见的 AE 为嗜睡（23%/患者年）、跌倒（17%）、外周水肿（14%）、恶心（12%）和贴剂部位反应（12%）。3%因贴剂部位反应停药。26%的患者未起始左旋多巴；其中起始左旋多巴的患者中，不到一半在第一年起始。25%的患者报告出现异动症；大多数（83%）在起始左旋多巴后首次出现。在长达 2 年的开放标签治疗期间，UPDRSⅡ+Ⅲ 总分均值始终低于双盲基线。
这是迄今为止罗替高汀开展的最长干预性研究。罗替高汀透皮贴剂最长达 6 年的治疗总体耐受性良好；报告的 AE 与短期研究观察到的相似，仅导致 24%的患者停药。
