恩他卡朋治疗帕金森病的多中心、随机、双盲、安慰剂对照临床研究

A randomized,placebo-controlled,double-blind,parallel-group trial of entacapone in patients with fluctuating Parkinson's disease

目的 研究恩他卡朋作为左旋多巴的辅助药物治疗帕金森病患者剂末现象的疗效和安全性。方法 帕金森病伴剂末现象患者 2 0 9例的 12周、多中心、随机、双盲、安慰剂、平行分组对照临床试验。根据患者日记记录的“开”和“关”期时间、统一帕金森病评定量表 (UPDRS)各部分评分、研究者总体评估变化量表和左旋多巴每日剂量评定疗效。结果 恩他卡朋治疗 12周时意向性治疗(ITT)人群“开”的时间自基线的 (7 4± 1 8)h/d延长至 (9 1± 2 5 )h/d ;“关”的时间自基线的 (6 8±2 2 )h/d缩短至 (5 2± 2 8)h/d ;UPDRS Ⅲ平均得分自基线的 36 7± 11 3减少至 30 0± 14 4 ;左旋多巴每日剂量 (mg/d)自基线的 5 89 2± 2 6 4 3减少至 4周的 5 6 1 5± 2 4 8 1;总体评估变化量表检查显示 6 9 9%的医生主观感觉到病情好转。与安慰剂组相比差异均有显著意义。常见的不良事件是多巴胺能反应 ,但是与安慰剂组相比差异均无显著意义。结论 恩他卡朋是有效而安全的治疗帕金森病伴剂末现象的辅助药物。

Objective To study the efficacy and safety of entacapone as an adjunct to levodopa treatment in pakinsonian patients with wearing-off motor fluctuations. Methods A total 209 pakinsonian patients with end-of-dose deterioration participated in a multi-center,12-weeks randomized,placebo-controlled,double blind,parallel-group trial.The efficacy of entacapone was assessed using the patient’s diary card,the Unified Parkinson’s Disease Rating Scale (UODRS) score,the daily levodopa dosage,and the global assessment of changes.Results 96.2% of the entacapone and 92.4% of the placebo-treated patients completed the study.In 209 cases of the ITT population,in comparison to the placebo-treated patients,entacapone had increased the mean “on” time (h/d) from 7.4±1.8 in base-line to 9.1±2.5 in week 12,decreased the “fof” time (from 6.8±2.2 in base-line to 5.2±2.8 in week 12),improved the motor scores (from 36.7±11.3 in base-line to 30.0±14.4 in week 12),and reduced the levodopa dose (from 589.2±264.3 in base-line to 561.5±248.1 in week 4). The improvement was also evident on impression of successful treatment for 69.9% of neurologists through global change assessment.There was no significant difference in the frequency of dopaminergic adverse events and serious laboratory abnormalities between entacapone and placebo groups.Conclusion The results of this study demonstrate that entacapone,the COMT inhibitor is a safe and effective extender of levodopa treatment for Parkinson’s disease patients with motor flucturations.