Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, INSERM CIC9302-UMR825 Toulouse, France.
Mov Disord. 2010 Oct 30;25(14):2326-32. doi: 10.1002/mds.23262.
The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.
本文旨在测试在早期帕金森病（PD）中，将即刻释放（IR）普拉克索转换为新的每日一次延长释放（ER）制剂的可行性。单独或与左旋多巴一起使用 IR 普拉克索每日三次治疗早期 PD 的非波动患者，被随机在一夜之间转换为 IR 每日三次（N=52）或 ER 每日一次（N=104），初始剂量不变。成功转换（定义为与基线 UPDRS II+III 评分相比没有恶化>15%且无药物相关不良事件退出）在 9 周（主要终点）和 4 周（调整前）进行评估。其他次要终点包括根据临床或患者总体印象（CGI/PGI）进行调整后的 UPDRS 评分和应答者比例的基线变化。用 ER 与 IR 的成功转换率之间的绝对差值来检验 ER 的非劣效性，定义为 95%置信区间下限不超过-15%。在 9 周时，84.5%的 ER 组成功转换，IR 组为 94.2%。未显示非劣效性，差异为-9.76%（95%CI：[-18.81%，+1.66%]）。在 4 周时，81.6%的 ER 组成功转换，IR 组为 92.3%，差异为-10.75%（95%CI：[-20.51%，+1.48%]）。UPDRS 变化和 CGI/PGI 分析显示两组之间无差异。两种制剂均安全且耐受良好。普拉克索 ER 与 IR 不相当，但差异较小。超过 80%的患者在未改变剂量的情况下成功地在一夜之间转换，这表明这种做法在大多数患者中是可行的。
