Samelisant(Samelisant) - 药物靶点：H3 receptor_在研适应症：猝倒症，发作性睡病，认知功能障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

H3 receptor

作用机制

H3 receptor拮抗剂(组胺H3受体拮抗剂)

治疗领域

神经系统疾病其他疾病

在研适应症

猝倒症发作性睡病认知功能障碍

非在研适应症-

原研机构

Suven Life Sciences Ltd.

在研机构

Suven Life Sciences Ltd.

非在研机构-

最高研发阶段临床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C21H31N3O3

InChIKeyLNXDUSQEXVQFGP-UHFFFAOYSA-N

CAS号1394808-82-2

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关联

4

项与 Samelisant 相关的临床试验

NCT04072380

/ Completed临床2期

A Phase 2, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 mg and 4 mg SUVN-G3031 Compared to Placebo in Patients With Narcolepsy With and Without Cataplexy

This study is of an investigational drug called SUVN-G3031 (Samelisant) as a possible treatment for narcolepsy with cataplexy or narcolepsy without cataplexy. The main purpose of this study is to learn how well the study drug works and how safe the study drug is compared to placebo.

开始日期2019-09-21

申办/合作机构

Suven Life Sciences Ltd.

NCT02881294

/ Completed临床1期

A Phase I, Single-center, Open-label, Single-dose Study to Evaluate the Effect of Food, Gender, and Age on the Pharmacokinetic Profile of Orally Administered SUVN-G3031 in Healthy Subjects

The purpose of the study is to investigate the effect of Food, Gender, and Age on the Pharmacokinetic Profile of SUVN-G3031 in Healthy Subjects

开始日期2016-08-01

申办/合作机构

Suven Life Sciences Ltd.

NCT02342041

/ Completed临床1期

A Single-center, Double-blind, Placebo-controlled, Randomized, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SUVN-G3031 After Single Ascending Doses and Multiple Ascending Doses in Healthy Male Subjects

The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of SUVN-G3031 in healthy male subjects following single or multiple ascending doses.

开始日期2014-09-01

申办/合作机构

Suven Life Sciences Ltd.

100 项与 Samelisant 相关的临床结果

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100 项与 Samelisant 相关的转化医学

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100 项与 Samelisant 相关的专利（医药）

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7

项与 Samelisant 相关的文献（医药）

2024-12-01·Sleep Medicine

Samelisant (SUVN-G3031), a histamine 3 receptor inverse agonist: Results from the phase 2 double-blind randomized placebo-controlled study for the treatment of excessive daytime sleepiness in adult patients with narcolepsy

Article

作者: Kalaikadhiban, Ilayaraja ; Jetta, Satish ; Dogiparti, Dhanunjay Kumar ; Mohammed, Abdul Rasheed ; Shinde, Anil ; Bogan, Richard K. ; Pandey, Santosh Kumar ; Jasti, Venkat ; Chowdary Palacharla, Veera Raghava ; Abraham, Renny ; Benade, Vijay ; Bogan, Richard K ; Subramanian, Ramkumar ; Jayarajan, Pradeep ; Goyal, Vinod Kumar ; Ravula, Jyothsna ; Nirogi, Ramakrishna

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12 min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5 % patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

2021-06-01·Psychopharmacology3区 · 医学

Samelisant (SUVN-G3031), a potent, selective and orally active histamine H3 receptor inverse agonist for the potential treatment of narcolepsy: pharmacological and neurochemical characterisation

3区 · 医学

Article

作者: Subramanian, Ramkumar ; Badange, Rajesh ; Jasti, Venkat ; Jayarajan, Pradeep ; Daripelli, Saivishal ; Shinde, Anil ; Petlu, Surendra ; Benade, Vijay ; Kamuju, Venkatesh ; Muddana, Nageswara Rao ; Bhyrapuneni, Gopinadh ; Mekala, Venkat Reddy ; Nirogi, Ramakrishna

RATIONALESamelisant (SUVN-G3031) is a potent and selective histamine H3 receptor (H3R) inverse agonist with good brain penetration and oral bioavailability.OBJECTIVESPharmacological and neurochemical characterisation to support the utility of Samelisant (SUVN-G3031) in the treatment of sleep-related disorders like narcolepsy.METHODSSamelisant (SUVN-G3031) was tested in rat brain microdialysis studies for evaluation of modulation in histamine, dopamine and norepinephrine. Sleep EEG studies were carried out in orexin knockout mice to study the effects of Samelisant (SUVN-G3031) on the sleep-wake cycle and cataplexy.RESULTSSamelisant (SUVN-G3031) has a similar binding affinity towards human (hH3R; K_i = 8.7 nM) and rat (rH3R; K_i = 9.8 nM) H3R indicating no inter-species differences. Samelisant (SUVN-G3031) displays inverse agonist activity and it exhibits very high selectivity towards H3R. Samelisant (SUVN-G3031) treatment in mice produced a dose-dependent increase in tele-methylhistamine levels indicating the activation of histaminergic neurotransmission. Apart from increasing the levels of histamine, Samelisant (SUVN-G3031) also modulates dopamine and norepinephrine levels in the cerebral cortex while it has no effects on dopamine levels in the striatum or nucleus accumbens. Treatment with Samelisant (SUVN-G3031; 10 and 30 mg/kg, p.o.) produced a significant increase in wakefulness with a concomitant decrease in NREM sleep in orexin knockout mice subjected to sleep EEG. Samelisant (SUVN-G3031) also produced a significant decrease in Direct REM sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy. Modulation in cortical levels of histamine, norepinephrine and dopamine provides the neurochemical basis for wake-promoting and anticataplectic effects observed in orexin knockout mice.CONCLUSIONSPre-clinical studies of Samelisant (SUVN-G3031) provide a strong support for utility in the treatment of sleep-related disorders related to EDS and is currently being evaluated in a phase 2 proof of concept study in the USA for the treatment of narcolepsy with and without cataplexy.

2021-06-01·Journal of Psychopharmacology3区 · 医学

Histamine 3 receptor inverse agonist Samelisant (SUVN-G3031): Pharmacological characterization of an investigational agent for the treatment of cognitive disorders

3区 · 医学

Article

作者: Shinde, Anil ; Jayarajan, Pradeep ; Ganuga, Narender ; Petlu, Surendra ; Manoharan, Arunkumar ; Bhyrapuneni, Gopinadh ; Jasti, Venkat ; Medapati, Rajesh B ; Subramanian, Ramkumar ; Abraham, Renny ; Badange, Rajesh K ; Benade, Vijay ; Nirogi, Ramakrishna ; Grandhi, Venkata R ; Gandipudi, Sudhakar

Background: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors. Aim: The aim of this research is to study the effects of Samelisant in diverse animal models of cognitive functions. Methods: The effects of Samelisant on cognitive functions were studied using social recognition, object recognition and Morris water maze tasks. Neurochemical and electrophysiological effects of Samelisant were monitored using microdialysis and electroencephalography techniques. Results: Samelisant showed procognitive effects in diverse animal models of cognition at doses ranging from 0.3 to 3 mg/kg, per os ( p.o.) (social recognition and object recognition task). Samelisant significantly increased the brain acetylcholine levels in the cortex at doses of 10 and 20 mg/kg, p.o. In the Morris water maze task, combined administration of suboptimal doses of Samelisant and donepezil resulted in procognitive effects significantly larger than the either treatment. Similarly, Samelisant significantly potentiated the effects of donepezil on pharmacodynamic biomarkers of cognition i.e. acetylcholine levels in brain and neuronal theta oscillations. Conclusion: Samelisant may have potential utility in the treatment of cognitive deficits associated with hypocholinergic state.

100 项与 Samelisant 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14835

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
猝倒症	临床2期	加拿大	Suven Life Sciences Ltd.	2019-09-21
猝倒症	临床2期	美国	Suven Life Sciences Ltd.	2019-09-21
认知障碍	临床2期	美国	Suven Life Sciences Ltd.	2014-09-01
发作性睡病	临床2期	-	Suven Life Sciences Ltd.	-
认知功能障碍	临床1期	美国	Suven Life Sciences Ltd.	-

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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


NCT04072380 (SUVN-G3031, CTgov)	临床2期	猝倒症	190	SUVN-G3031 (SUVN-G3031 2mg)	(淵顧壓憲遞憲簾網淵製) = 簾鏇範積鹹艱鬱顧願淵艱製淵積鑰鏇憲餘壓鏇 (簾壓齋鑰淵簾顧衊鏇鹹, 衊衊選夢繭窪選窪簾糧 ~ 願夢餘憲鏇衊醖願觸襯) 更多	-	2025-01-13
NCT04072380 (SUVN-G3031, CTgov)	临床2期	猝倒症	190	SUVN-G3031 (SUVN-G3031 4mg)	(淵顧壓憲遞憲簾網淵製) = 鑰憲淵選蓋鏇積衊憲積艱製淵積鑰鏇憲餘壓鏇 (簾壓齋鑰淵簾顧衊鏇鹹, 積獵醖鹹觸鹽鹹醖夢網 ~ 餘製淵簾夢簾糧壓夢選) 更多	-	2025-01-13
NCT02342041 \| NCT04072380 (Pubmed \| Clin Drug Investig)	临床1/2期	发作性睡病	-	SUVN-G3031	網壓獵憲網衊積顧廠廠(觸顧鬱簾製願膚憲糧齋) = 窪餘齋壓鏇蓋糧選壓廠願艱繭壓艱艱襯遞鑰觸 (網蓋蓋積醖網簾簾獵衊 )	-	2020-07-01
NCT04072380 (SUVN-G3031, WSC2019)	临床2期	发作性睡病	-	SUVN-G3031	積簾觸構顧構壓願鑰壓(憲鏇觸蓋膚鏇醖選願鑰) = indicated superior wake promoting profile of SUVN-G3031 選鏇壓獵襯膚鏇觸製觸 (餘鹽鏇壓窪願鹽觸繭鑰 ) 更多	积极	2019-09-20
NCT04072380 (SUVN-G3031, AAIC2014)	临床2期	认知功能障碍	-	SUVN-G3031	築艱顧夢膚衊壓淵醖網(積醖顧觸膚願餘鑰製廠) = 構鏇襯顧築膚鹽簾糧構獵鏇製醖鬱鑰範鹽餘蓋 (鏇積遞觸淵窪積醖鏇蓋 ) 更多	-	2014-07-01