Lew Mark F, Pahwa Rajesh, Leehey Maureen, Bertoni John, Kricorian Greg
Keck/University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Curr Med Res Opin. 2007 Apr;23(4):741-50. doi: 10.1185/030079906x167697.
Patients receiving levodopa for Parkinson's disease experience motor fluctuations and immobility ('off' episodes) between doses. This study assessed adjunctive Zelapar (selegiline orally disintegrating tablet (ODT)) for managing off episodes and for long-term safety.
This open-label extension evaluated long-term safety, efficacy, and tolerability of adjunctive selegiline ODT 2.5 mg in patients who completed either of two large phase 3 double-blind studies. The study was to end after 12 months but was amended to be open-ended. Investigators could increase levodopa doses and introduce controlled-release formulations of levodopa or dopamine agonists if warranted. Additionally, results of a small randomized trial of open-label selegiline ODT 1.25 mg in comparison to conventional selegiline was added only to the safety analysis. Efficacy variables included changes in daily off time and Patient's Global Impression of Improvement (PGI-I) and Clinical Global Impressions Severity of Disease (CGI-S) ratings. Safety assessments included adverse events and oropharyngeal findings.
This study enrolled 254 patients: 248 from the large phase 3 studies (efficacy analysis) and an additional six from the prior open-label comparison (safety analysis) in order to evaluate a larger population for safety purposes. Mean reduction from baseline in daily off time was 9.4% (1.6 h) for patients previously given selegiline ODT, 6.0% (1.2 h) for those switched from placebo, and 8.1% (1.4 h) overall. PGI-I and CGI-S ratings indicated little or no change from baseline. Treatment-related adverse events occurred in 132 (52%) patients. No severe oral irritations were attributed to selegiline ODT or prompted discontinuation.
Long-term selegiline ODT 2.5 mg/day was effective, safe, and well tolerated in patients with Parkinson's disease experiencing off episodes during levodopa therapy.
帕金森病患者接受左旋多巴治疗时会出现剂末运动波动和静止不动（“关”期）。本研究评估了辅助使用Zelapar（司来吉兰口腔崩解片（ODT））治疗“关”期及长期安全性。
这项开放标签扩展研究评估了辅助使用2.5毫克司来吉兰口腔崩解片对完成两项大型3期双盲研究之一的患者的长期安全性、疗效和耐受性。该研究原计划在12个月后结束，但修改为无固定期限。如有必要，研究人员可增加左旋多巴剂量，并引入左旋多巴控释制剂或多巴胺激动剂。此外，一项比较开放标签1.25毫克司来吉兰口腔崩解片与传统司来吉兰的小型随机试验结果仅纳入安全性分析。疗效变量包括每日“关”期时间变化、患者总体改善印象（PGI-I）和临床总体印象疾病严重程度（CGI-S）评分。安全性评估包括不良事件和口咽部检查结果。
本研究共纳入254例患者：248例来自大型3期研究（疗效分析），另外6例来自之前的开放标签对照研究（安全性分析），以便为安全性评估纳入更多患者。之前接受司来吉兰口腔崩解片治疗的患者每日“关”期时间较基线平均减少9.4%（1.6小时），从安慰剂转换过来的患者减少6.0%（1.2小时），总体减少8.1%（1.4小时）。PGI-I和CGI-S评分显示与基线相比变化很小或无变化。132例（52%）患者发生了与治疗相关的不良事件。没有严重的口腔刺激归因于司来吉兰口腔崩解片或导致停药。
对于左旋多巴治疗期间出现“关”期的帕金森病患者，长期每日服用2.5毫克司来吉兰口腔崩解片有效、安全且耐受性良好。
