莫达非尼与安非他命右旋苯丙胺治疗特发性嗜睡症和 2 型发作性睡病的随机、双盲、非劣效性试验。

Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.

机构信息

Department of Neurology, Emory University School of Medicine, 12 Executive Park Dr NE, Atlanta, GA, 30329, USA.

Emory Healthcare, Emory Sleep Center, Atlanta, GA, USA.

出版信息

CNS Drugs. 2024 Nov;38(11):909-920. doi: 10.1007/s40263-024-01122-y. Epub 2024 Sep 21.

DOI:10.1007/s40263-024-01122-y

PMID:39306601

Abstract

BACKGROUND AND OBJECTIVE

Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders.

METHODS

Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups.

RESULTS

Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine.

CONCLUSION

Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2.

REGISTRATION

Clinicaltrials.gov Registration (NCT03772314) 12/10/18. .

摘要

背景和目的

尽管有多种治疗方法可用于治疗 2 型发作性睡病和特发性嗜睡症，但仍需要研究安非他命、嗜睡以外的症状以及比较疗效。我们对莫达非尼与安非他命-右旋安非他命在这些疾病中的应用进行了一项随机、完全双盲、非劣效性试验。

方法

44 名成年人被随机分为莫达非尼或安非他命-右旋安非他命组，两组均接受个体化滴定治疗，莫达非尼最大剂量为每日 2 次、每次 200mg，安非他命-右旋安非他命最大剂量为每日 2 次、每次 20mg，疗程为 12 周。主要结局指标为从基线到第 12 周时 Epworth 嗜睡量表评分的变化，非劣效性界值为 2 分。次要结局指标包括：（1）患者对疾病严重程度、嗜睡、睡眠惯性和认知的总体变化的评估；（2）从基线到 Hypersomnia Severity Index 的变化；（3）从基线到 Sleep Inertia Questionnaire 的变化。比较两组之间的不良反应事件。

结果

莫达非尼组 Epworth 评分改善 5.0 [±标准偏差（SD）2.7]分，安非他命-右旋安非他命组改善 4.4（±SD 4.7）分，安非他命-右旋安非他命组未达到非劣效性（P=0.11）。安非他命-右旋安非他命在严重程度、嗜睡、睡眠惯性、Hypersomnia Severity Index 和 Sleep Inertia Questionnaire 的评分变化上也达到了非劣效性。莫达非尼组因不良反应事件而停药的比例为 31.8%（包括 2 例严重事件），安非他命-右旋安非他命组为 9.1%，P=0.13。莫达非尼组更常见焦虑，而安非他命-右旋安非他命组更常见食欲抑制。