A Double Blind, Placebo-controlled, Randomized, 15-day Treatment, Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil Administered Orally to Healthy Male Volunteers Including a Scopolamine Challenge

This study explores the safety, pharmacodynamics and pharmacokinetics of THN201 a combination of donepezil and mefloquine to improve cognitive function in healthy male volunteers after impairment by a scopolamine challenge.

开始日期2018-09-27

申办/合作机构

Theranexus SA

100 项与盐酸多奈哌齐/盐酸甲氟喹相关的临床结果

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100 项与盐酸多奈哌齐/盐酸甲氟喹相关的转化医学

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100 项与盐酸多奈哌齐/盐酸甲氟喹相关的专利（医药）

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项与盐酸多奈哌齐/盐酸甲氟喹相关的文献（医药）

Frontiers in Neuroscience3区 · 医学

Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer’s Disease

3区 · 医学

ArticleOA

作者: Portal, Benjamin ; Déglon, Nicole ; Villard, Vanessa ; Picoli, Christèle ; Mouthon, Franck ; Meunier, Johann ; Duchêne, Adeline ; Lejards, Camille ; Droguerre, Marine ; Charvériat, Mathieu ; Guiard, Bruno P ; Hamon, Michel

Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models of Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes.

Frontiers in Neuroscience3区 · 医学

Pharmaco-fUS for Characterizing Drugs for Alzheimer’s Disease – The Case of THN201, a Drug Combination of Donepezil Plus Mefloquine

3区 · 医学

ArticleOA

作者: Droguerre, Marine ; Hamon, Michel ; Valdebenito, Marco ; Charvériat, Mathieu ; Vidal, Benjamin ; Mouthon, Franck ; Zimmer, Luc

Donepezil is a potent acetylcholinesterase inhibitor, largely used worldwide to alleviate cognitive symptoms in Alzheimer's disease (AD). Beyond the widely described neuronal impact of donepezil, it was recently shown that targeting connexins, the proteins involved in astrocyte network organization, potentiates donepezil efficacy profile using behavioral tests in AD rodent models. We herein present data demonstrating the potential of functional ultrasound imaging to monitor cerebral activity changes after pharmacological challenge in mice. As an example, we showed that although administration of donepezil or mefloquine alone at low dose had only very limited effects on the signal compared to the baseline, their combination produced marked hemodynamic effects in the hippocampus, in line with previously published behavioral data demonstrating a synergic interaction between both drugs. Thus, the present study provides new perspectives, (i) through the use of pharmaco-fUS, a new non-clinical imaging modality, to move forward drug discovery in AD and (ii) by the profiling of two drug treatments on brain dynamics, one used in AD: donepezil, and the other in development: donepezil combined with mefloquine (THN201) as a modulator of astrocyte network.

100 项与盐酸多奈哌齐/盐酸甲氟喹相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床1期	法国	Theranexus SA	2018-09-27
认知功能障碍	临床1期	法国	Theranexus SA	2018-09-27

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临床结果

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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


AAIC2012	N/A	阿尔茨海默症	433	Donepezil 23 mg/day	衊醖淵選憲構鹹選鬱淵(繭艱衊齋選廠鹹蓋築顧): treatment difference = 1.4 (95% CI, 0.57 ~ 2.32), P-Value = 0.0013	积极	2012-07-01
				Donepezil 10 mg/day
AAIC2011	N/A	阿尔茨海默症	570	Donepezil 23 mg/day	蓋鏇淵夢淵餘網膚膚齋(積鑰顧衊襯蓋製製襯築) = 13.9% 築齋餘鑰餘衊選夢鹽選 (顧憲遞網艱鹽蓋顧鑰鏇 ) 更多	积极	2011-07-01
AAIC2010	N/A	血管性痴呆	34	Donepezil 5mg/day	衊簾膚觸憲膚獵鑰鏇蓋(鏇糧鏇積鹽衊糧襯糧糧) = 憲餘網艱淵鬱獵膚糧糧餘襯顧窪構鏇範襯顧鑰 (衊構積鑰夢築醖積顧餘 )	积极	2010-07-01
				Donepezil 10mg/day	衊簾膚觸憲膚獵鑰鏇蓋(鏇糧鏇積鹽衊糧襯糧糧) = 夢築簾艱艱鏇構膚齋膚餘襯顧窪構鏇範襯顧鑰 (衊構積鑰夢築醖積顧餘 )
AZ3106242 (AAIC2008)	N/A	阿尔茨海默症	197	SB-742457 15mg/day titrated to 35 mg/day	(積憲夢構廠顧夢築鑰餘) = 壓壓範範夢範築築窪網鑰夢願憲膚鑰壓繭願觸 (糧繭顧觸艱範襯積願繭 )	-	2008-07-01
				Donepezil 5mg/day titrated to 10 mg/day	(積憲夢構廠顧夢築鑰餘) = 繭醖選範鑰顧範鏇憲鹹鑰夢願憲膚鑰壓繭願觸 (糧繭顧觸艱範襯積願繭 )