氟卡尼/莫达非尼(Flecainide/Modafinil) - 药物靶点：DAT x SCNA_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Modafinil/flecainide

靶点

DAT x SCNA

作用方式

拮抗剂、调节剂

作用机制

DAT拮抗剂(多巴胺转运体拮抗剂)、SCNA调节剂(钠通道α亚基家族调节剂)

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病

在研适应症-

非在研适应症

发作性睡病帕金森病睡眠剥夺+ [1]

原研机构

Theranexus SA

在研机构-

非在研机构

Theranexus SA

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C19H24F6N2O5

InChIKeyRKXNZRPQSOPPRN-UHFFFAOYSA-N

CAS号54143-56-5

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关联

4

项与氟卡尼/莫达非尼相关的临床试验

NCT03624920

/ Completed临床2期

Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness

This is a randomized, placebo-controlled, 3-way cross-over phase IIa trial comparing two dose levels of THN102 to placebo in patients suffering from Parkinson's disease associated with excessive daytime sleepiness.

开始日期2018-07-12

申办/合作机构

Theranexus SA

EUCTR2017-004475-31-CZ

/ Not yet recruiting临床2期

Randomised, double-blind, placebo-controlled, complete 3-way cross-over phase IIa trial to investigate safety and efficacy of two THN102 doses in subjects with excessive daytime sleepiness associated with Parkinson’s disease

开始日期2018-05-09

申办/合作机构-

NCT02821715

/ Completed临床2期

Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

This Phase 2 study is a 8-site, double-blind, randomised, placebo-controlled, 3-way cross-over trial, involving 3 treatments with Modafinil 300 mg or the combination drug THN102 (Modafinil/Flecainide 300 /3 mg, Modafinil/Flecainide 300 /27 mg).

开始日期2016-09-01

申办/合作机构

Theranexus SA

100 项与氟卡尼/莫达非尼相关的临床结果

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100 项与氟卡尼/莫达非尼相关的转化医学

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100 项与氟卡尼/莫达非尼相关的专利（医药）

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3

项与氟卡尼/莫达非尼相关的文献（医药）

2022-02-01·Movement Disorders1区 · 医学

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial

1区 · 医学

Article

作者: Rein, Werner ; Thobois, Stéphane ; Ondo, William G. ; Corvol, Jean‐Christophe ; Pahwa, Rajesh ; Valis, Martin ; Dauvilliers, Yves ; Klostermann, Fabian ; Kovacs, Norbert ; Rascol, Olivier ; Bosse, Björn ; Defebvre, Luc ; Maltête, David ; Azulay, Jean‐Philippe ; Videnovic, Aleksandar

AbstractBackgroundExcessive 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.ObjectiveThe aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.MethodsThe 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.ResultsBoth 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.ConclusionsTHN102 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

2019-11-01·British Journal of Clinical Pharmacology2区 · 医学

Efficacy of THN102 (a combination of modafinil and flecainide) on vigilance and cognition during 40‐hour total sleep deprivation in healthy subjects: Glial connexins as a therapeutic target

2区 · 医学

Article

作者: Dubourdieu, Dominique ; Mouthon, Franck ; Dauvilliers, Yves ; Arnal, Pierrick ; Gomez‐Merino, Danielle ; Chennaoui, Mounir ; Brunner‐Ferber, Francoise ; Sauvet, Fabien ; Rein, Werner ; Erblang, Mégane ; Bougard, Clément ; Van Beers, Pascal ; Lefloch, Hervé ; Rabat, Arnaud ; Leger, Damien ; Charvériat, Mathieu ; Drogou, Catherine ; Bourrrilhon, Cyprien ; Guillard, Mathias

AimsTHN102 is a novel combination of modafinil and low‐dose flecainide, targeting glial connexin activity to modulate modafinil effects. We investigated THN102 efficacy compared to modafinil and to placebo on vigilance and cognitive function during 40‐hour total sleep deprivation (TSD).MethodsTwenty healthy men participated in a double‐blind, randomized, incomplete‐block 3‐period cross‐over trial with 5 treatments (n = 12 per group): placebo (PBO), modafinil 100 mg (MOD100), THN102 100/1, 100/3, 100/9 (modafinil 100 mg and flecainide 1, 3 or 9 mg). Each period included a baseline day and a TSD day with treatments administered 3 times (01:00, 09:00 and 19:00). Reaction time in psychomotor vigilance test, subjective somnolence and vital signs were assessed before and during treatment. Working memory (2‐Back) and executive processes (Go/noGo for vigilance and inhibition, Wisconsin card sorting task for mental flexibility, and Tower of London test for planning) were evaluated at 16:30.ResultsAt 5 hours postdose−1 (after 23 hours TSD, primary endpoint), THN102 100/1 resulted in statistically higher psychomotor vigilance test speed vs MOD100 (3.97 ± 0.09 vs 3.74 ± 0.14, P < .05). No increase in effect was observed with higher flecainide doses in combinations. Most THN102 doses vs MOD100 also improved the number of correct responses in 2‐Back and Go errors in Go/noGo (P < .05 for all doses), and perseverative responses in Wisconsin card sorting task (for 100/1 and 100/9). No impact on cardiac conduction was noted with THN102, and safety was similar to MOD100.ConclusionsTHN102 seems more efficient than modafinil on vigilance, working memory and executive functions, opening new perspectives in management of hypersomnolence disorders.

2018-07-01·International Journal of Neuropsychopharmacology2区 · 医学

Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination

2区 · 医学

ArticleOA

作者: Dauvilliers, Yves ; Lin, Jian-Sheng ; Vodovar, Dominique ; Mouthon, Franck ; Charvériat, Mathieu ; Duchêne, Adeline ; Leroy, Claire ; Wimberley, Catriona ; Tournier, Nicolas ; Pottier, Géraldine ; Giaume, Christian

BackgroundModafinil, a nonamphetaminic wake-promoting compound, is prescribed as first line therapy in narcolepsy, an invalidating disorder characterized by excessive daytime sleepiness and cataplexy. Although its mode of action remains incompletely known, recent studies indicated that modafinil modulates astroglial connexin-based gap junctional communication as administration of a low dose of flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and procognitive activity of modafinil in rodents and healthy volunteers. The aim of this study is to investigate changes in glucose cerebral metabolism in rodents, induced by the combination of modafinil+flecainide low dose (called THN102).MethodsThe impact of THN102 on brain glucose metabolism was noninvasively investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography imaging in Sprague-Dawley male rats. Animals were injected with vehicle, flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D-glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to a rat brain template and normalized from the total brain Positron Emission Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software. Comparison of brain glucose metabolism between groups was then performed.ResultsTHN102 significantly increased regional brain glucose metabolism as it resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in the cortex, striatum, and amygdala compared with control or drugs administered alone. These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102.ConclusionData presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients.

100 项与氟卡尼/莫达非尼相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床2期	捷克	Theranexus SA	2018-07-12
帕金森病	临床2期	法国	Theranexus SA	2018-07-12
帕金森病	临床2期	美国	Theranexus SA	2018-07-12
帕金森病	临床2期	德国	Theranexus SA	2018-07-12
帕金森病	临床2期	匈牙利	Theranexus SA	2018-07-12
发作性睡病	临床2期	比利时	Theranexus SA	2016-09-01
发作性睡病	临床2期	法国	Theranexus SA	2016-09-01
嗜睡	临床2期	法国	Theranexus SA	2016-09-01
嗜睡	临床2期	比利时	Theranexus SA	2016-09-01
睡眠剥夺	临床2期	-	Theranexus SA	2015-09-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03624920 (CTgov)	临床2期	发作性睡病 \| 帕金森病	77	Placebo+THN102 (Placebo)	憲網淵壓夢構遞夢鑰獵(襯衊糧憲簾積鏇繭獵鹽) = 構蓋糧憲膚遞淵齋醖壓蓋遞鏇選網網願範獵鬱 (鹽壓餘觸醖艱齋觸夢衊, 窪餘願蓋艱醖觸簾顧齋 ~ 壓網鏇糧糧鹽構鏇積鹽) 更多	-	2020-12-01
				THN102 (THN102 200/2)	憲網淵壓夢構遞夢鑰獵(襯衊糧憲簾積鏇繭獵鹽) = 構鑰醖膚膚淵簾築襯蓋蓋遞鏇選網網願範獵鬱 (鹽壓餘觸醖艱齋觸夢衊, 遞鏇願鹹醖淵遞顧選獵 ~ 範淵蓋範製蓋淵壓網齋) 更多
NCT02821715 (CTgov)	临床2期	发作性睡病 \| 嗜睡	51	Active comparator: Modafinil + placebo (Modafinil + Placebo)	餘夢觸鹹鏇夢糧選築壓(襯壓獵襯齋齋蓋鹹餘鹹) = 鬱觸構構廠鑰獵淵構鏇窪獵窪鹽膚窪鏇鹽艱夢 (顧壓衊膚構壓築網鏇顧, 選選獵願範鏇鬱製積壓 ~ 襯鏇鑰齋顧網鑰壓齋網) 更多	-	2020-09-04
				THN102 300/3 (THN102 300/3)	餘夢觸鹹鏇夢糧選築壓(襯壓獵襯齋齋蓋鹹餘鹹) = 獵鬱築製網顧鏇願艱築窪獵窪鹽膚窪鏇鹽艱夢 (顧壓衊膚構壓築網鏇顧, 艱壓鹽淵蓋蓋鬱遞觸構 ~ 夢鹽遞廠選築鑰餘齋構) 更多