Kim Jong-Min, Chung Sun Ju, Kim Jae Woo, Jeon Beom Seok, Singh Pritibha, Thierfelder Stephan, Ikeda Junji, Bauer Lars
Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea.
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
BMC Neurol. 2015 Feb 28;15:17. doi: 10.1186/s12883-015-0267-7.
Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA.
PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time.
Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC.
Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit.
ClinicalTrials.gov identifier NCT01723904 . Trial registration date: November 6, 2012.
在临床实践中，以最小的副作用实现最佳症状控制是一个主要目标。帕金森病（PD）的双药多巴胺受体激动剂（DA）疗法可能是一种很有前景的治疗方法，因为不同药代动力学/药理学特性的组合可能导致对高剂量的需求降低，因此耐受性良好。本研究的目的是调查在左旋多巴和低剂量口服DA治疗效果不佳的晚期PD患者中，罗替戈汀透皮系统作为口服DA的附加治疗的安全性和有效性。
PD0015是一项针对晚期PD合并睡眠障碍或清晨运动障碍患者的开放标签、多国研究。患者在1 - 4周内滴定至最佳剂量的罗替戈汀（≤8毫克/24小时），并维持4 - 7周（8周治疗期）。左旋多巴和口服DA（普拉克索≤1.5毫克/天，罗匹尼罗≤6.0毫克/天）的剂量保持稳定。主要变量是临床总体印象（CGI）第4项：副作用，用于评估安全性。其他变量包括不良事件（AE）、患者总体变化印象（PGIC）、统一帕金森病评定量表（UPDRS）II和III、帕金森病睡眠量表（PDSS - 2）、匹兹堡睡眠质量指数（PSQI）以及“关”期时间。
在90例接受罗替戈汀治疗的患者中，79例（88%）完成了研究；5例（6%）因不良事件退出。大多数（83/89；93%）的CGI - 4评分<3，表明罗替戈汀附加治疗不影响功能；6例（7%）经历了影响功能的药物相关不良事件（评分≥3）。发生率≥5%的不良事件有用药部位瘙痒（13%）、头晕（10%）、体位性低血压（10%）、恶心（8%）、运动障碍（8%）和鼻咽炎（6%）。观察到运动功能（UPDRS III）、日常生活活动能力（UPDRS II）、睡眠障碍（PDSS - 2、PSQI）有数值改善，“关”期时间减少。大多数（71/88；81%）患者在PGIC上有改善。
在晚期PD患者中，将罗替戈汀透皮系统添加到低剂量口服DA治疗中是可行的，并且可能带来临床益处。
ClinicalTrials.gov标识符NCT01723904。试验注册日期：2012年11月6日。
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