Corvol Jean-Christophe, Azulay Jean-Philippe, Bosse Björn, Dauvilliers Yves, Defebvre Luc, Klostermann Fabian, Kovacs Norbert, Maltête David, Ondo William G, Pahwa Rajesh, Rein Werner, Thobois Stéphane, Valis Martin, Videnovic Aleksandar, Rascol Olivier
Department of Neurology, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Paris Brain Institute-ICM, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
Department of Neurology and Movement Disorders, La Timone Hospital, Assistance Publique-Hôpitaux de Marseille, NS-PARK/FCRIN Network, Marseille, France.
Mov Disord. 2022 Feb;37(2):410-415. doi: 10.1002/mds.28840. Epub 2021 Oct 28.
Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide.
The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.
The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score.
Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage.
THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society.
日间过度嗜睡（EDS）是帕金森病（PD）常见且致残的症状，尚无获批的治疗方法。THN102是一种新型的莫达非尼与低剂量氟卡尼的复方药物。
本研究旨在评估THN102治疗伴有EDS的PD患者的安全性和有效性。
该方法采用随机、双盲、安慰剂对照、交叉试验，比较两种剂量的THN102（200mg/d莫达非尼与2mg/d[200/2]或18mg/d氟卡尼[200/18]）与安慰剂；75例患者接受治疗。主要终点是安全性。主要疗效指标是爱泼沃斯嗜睡量表（ESS）评分的变化。
两种剂量的THN102耐受性均良好。THN102 200/2组ESS显著改善（最小二乘均值与安慰剂比较[95%置信区间，CI]：-1.4[-2.49；-0.31]，P = 0.012），但200/18剂量组无显著变化。
THN102耐受性良好，在200/2剂量时显示出疗效信号，支持进一步研发用于治疗PD患者的EDS。©2021国际帕金森和运动障碍协会。
