Pitolisant与安慰剂或莫达非尼在发作性睡病患者中的疗效:一项双盲随机试验。
文章的细节
-
引用
复制到剪贴板 -
Dauvilliers Y, Bassetti C, Lammers GJ, Arnulf I, Mayer G, Rodenbeck A, Lehert P, Ding CL, Lecomte JM, Schwartz JC
Pitolisant与安慰剂或莫达非尼在发作性睡病患者中的疗效:一项双盲随机试验。
《柳叶刀神经杂志》2013年11月12日(11):1068-75。doi: 10.1016 / s1474 - 4422(13) 70225 - 4。Epub 2013年10月7日。
- PubMed ID
-
24107292 (PubMed视图］
- 摘要
-
背景:嗜睡症的特征是白天过度嗜睡(EDS)和猝倒。组胺神经元对保持清醒至关重要。我们评估了pitolisant(以前称为BF2.649)在发作性睡病患者中的安全性和有效性，pitolisant是一种选择性组胺H3受体逆激动剂，可激活这些神经元。方法:在这项双盲、随机、平行组对照试验中，我们从5个欧洲国家的32个睡眠障碍中心招募了嗜睡症患者。如果患者年龄在18岁或以上，至少14天没有服用精神兴奋剂，并且患有EDS(定义为Epworth嗜睡量表[ESS]至少14分)，则符合条件。使用计算机生成的随机序列，我们随机分配患者接受匹唑仑、莫达非尼或安慰剂(1:1:1)。治疗持续8周:3周根据研究者判断灵活给药(每天10 mg, 20 mg，或40 mg pitolisant;每天100毫克，200毫克或400毫克莫达非尼)，然后稳定给药5周。患者每天服用4片，采用双假人设计，以确保掩蔽。对于初步分析，在意向治疗人群中进行评估，我们评估了皮唑啉剂与安慰剂的优势，以及皮唑啉剂与莫达非尼的非劣势。 This trial is registered with ClinicalTrials.gov, number NCT01067222. FINDINGS: Between May 26, 2009, and June 30, 2010, we screened 110 patients, 95 of whom were eligible and randomly assigned to treatment: 30 to placebo, 32 to pitolisant, and 33 to modafinil. Over the 8-week treatment period, mean ESS score reductions were -3.4 (SD 4.2) in the placebo group, -5.8 (6.2) in the pitolisant group, and -6.9 (6.2) in the modafinil group. Our primary analysis of between-group differences in mean ESS score at endpoint (adjusted for baseline) showed pitolisant to be superior to placebo (difference -3.0, 95% CI -5.6 to -0.4; p=0.024), but not non-inferior to modafinil (difference 0.12, 95% CI -2.5 to 2.7; p=0.250). We recorded 22 adverse events with pitolisant, 26 with modafinil, and ten with placebo. Six severe adverse events were treatment-related: one with pitolisant (abdominal discomfort) and five with modafinil (abdominal pain, abnormal behaviour, amphetamine-like withdrawal symptoms, lymphoadenopathy, and inner ear disorders). INTERPRETATION: Pitolisant at doses up to 40 mg was efficacious on EDS compared with placebo and well tolerated compared with modafinil. If these findings are substantiated in further studies, pitolisant could offer a new treatment option for patients with narcolepsy. FUNDING: Bioprojet, France.
引用本文的药物库数据
- 药物