ASP-8302(ASP-8302) - 药物靶点：M3 receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

M3 receptor

作用机制

M3 receptor调节剂(毒蕈碱型乙酰胆碱受体M3 调节剂)

治疗领域

泌尿生殖系统疾病

在研适应症-

非在研适应症

膀胱功能不全

原研机构

Astellas Pharma, Inc.

在研机构-

非在研机构

Astellas Pharma Europe Ltd.

Astellas Pharma, Inc.

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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关联

3

项与 ASP-8302 相关的临床试验

NCT03702777 / Completed临床2期

A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2a, Proof-of-Concept Study of ASP8302 in Subjects With Underactive Bladder

The study objectives of this study are to evaluate the efficacy of ASP8302 compared with placebo in participants with underactive bladder (UAB), to investigate the safety and tolerability of ASP8302 compared with placebo in participants with UAB, to investigate the pharmacokinetics of ASP8302 in participants with UAB and to support the development of the UAB - Patient Reported Outcome (PRO).

开始日期2018-11-20

申办/合作机构

Astellas Pharma Europe Ltd.

EUCTR2017-003693-13-PL / Not yet recruiting临床2期

A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2a, Proof-of-Concept Study of ASP8302 in Subjects with Underactive Bladder

开始日期2018-10-18

申办/合作机构

Astellas Pharma Europe Ltd.

NCT03361540 / Completed临床1期

A Placebo-controlled, Single and Multiple Ascending Oral Dose Study in Non-elderly Healthy Japanese Male and Female Subjects

The objective of this study is to evaluate the safety, tolerability and pharmacokinetic of single/multiple ascending oral doses of ASP8302 in non-elderly healthy Japanese male and female subjects.

开始日期2017-11-14

申办/合作机构

Astellas Pharma, Inc.

100 项与 ASP-8302 相关的临床结果

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100 项与 ASP-8302 相关的转化医学

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100 项与 ASP-8302 相关的专利（医药）

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4

项与 ASP-8302 相关的文献（医药）

2024-10-01·Clinical Pharmacology in Drug Development

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M₃ Receptor‐Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers

Article

作者: Michon, Ingrid ; Aarden‐Bakker, Marlous ; Osaki, Fumio ; van Till, Jan Willem Olivier ; Treijtel, Nicoline ; Miyatake, Daisuke ; Sekino, Hisakuni ; Saito, Masako ; de Vries, Michiel ; Takusagawa, Shin ; Guro, Sayuri ; Kuroishi, Kentaro ; Groenendaal‐van de Meent, Dorien ; Fadini, Tomasso

AbstractASP8302 is an orally administered positive allosteric modulator of the muscarinic M3 receptor. Two Phase 1 studies were conducted, a first‐in‐human study in Europe and a Japanese phase 1 study. Both were randomized, participant‐ and investigator‐blinded, placebo‐controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment‐emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first‐in‐human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose‐dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development.

2022-07-01·LUTS: Lower Urinary Tract Symptoms4区 · 医学

Muscarinic M₃ positive allosteric modulator ASP8302 enhances bladder contraction and improves voiding dysfunction in rats

4区 · 医学

Article

作者: Okimoto, Risa ; Ohtake, Akiyoshi ; Imazumi, Katsunori ; Takeda, Masahiro ; Ino, Katsutoshi ; Sakamoto, Kazuyuki ; Takamatsu, Hajime ; Masuda, Noriyuki ; Ishizu, Kenichiro ; Yuyama, Hironori

AbstractObjectivesMuscarinic M3 (M3) receptors mediate cholinergic smooth muscle contraction of the bladder. Current drugs targeting bladder M3 receptors for micturition disorders have a risk of cholinergic side effects due to excessive receptor activation and insufficient selectivity. We investigated the effect of ASP8302, a novel positive allosteric modulator (PAM) of M3 receptors, on bladder function in rats.MethodsModulation of carbachol‐induced increases in intracellular Ca2+ was assessed in cells expressing rat muscarinic receptors. Potentiation of bladder contractions was evaluated using isolated rat bladder strips and by measuring intravesical pressure in anesthetized rats. Conscious cystometry was performed to investigate the effects on residual urine volume and voiding efficiency in rat voiding dysfunction models induced by the α1‐adrenoceptor agonist midodrine and muscarinic receptor antagonist atropine, and bladder outlet obstruction. To assess potential side effects, the number of stools and tracheal insufflation pressure were measured in conscious and anesthetized rats, respectively.ResultsASP8302 demonstrated PAM effects on the rat M3 receptor in cell assays, and augmented cholinergic bladder contractions both in vivo and in vitro. ASP8302 improved voiding efficiency and reduced residual urine volume in two voiding dysfunction models as effectively as distigmine bromide, but unlike distigmine bromide did not affect the number of stools or tracheal insufflation pressure.ConclusionsOur results in rats indicate that ASP8302 improves voiding dysfunction by potentiating bladder contraction with fewer effects on cholinergic responses in other organs, and suggest a potential advantage over current cholinomimetic drugs for treating micturition disorders caused by insufficient bladder contraction.

2022-06-01·Neurourology and Urodynamics3区 · 医学

Muscarinic‐3‐receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial

3区 · 医学

Article

作者: Chapple, Christopher R. ; van Koeveringe, Gommert A. ; Arita, Eri ; Abrams, Paul ; Croy, Richard ; Oelke, Matthias ; van Till, Jan Willem Olivier ; Yamaguchi, Osamu ; Kuroishi, Kentaro

AbstractAimThe aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3‐PAM), in patients with underactive bladder (UAB).MethodsA randomized, double‐blind, placebo‐controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4‐week oral once‐daily administration of 100 mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVRC2). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressure‐flow studies were performed in a subgroup.ResultsOne hundred and thirty‐five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVRC2 was −40.0 ml (ASP8302) versus −35.0 ml (placebo) and the difference between groups was −5.0 ml (p = 0.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (Qmax) and detrusor pressure at Qmax (Pdet.Qmax) increased (mean difference in change ASP8302 vs. placebo: 3.8 ml/s, p = 0.031 and 12.7 cm H2O, p = 0.034, respectively). Urinary incontinence episodes/24 h decreased in males with preexisting incontinence (mean difference: −0.35; p = 0.028). The incidence of adverse events was similar between study groups (ASP8302: 33.3%, placebo: 31.4%). In the included subjects, both baseline urine flow and bladder voiding pressure was low. Compared with PVR, simultaneous BVE measurements were more consistent between various methods (spontaneous vs. standardized bladder filling, catheterization vs. ultrasound [US]).ConclusionsASP8302 was safe and well tolerated in patients with UAB identified by nonurodynamic clinical criteria, but it did not show efficacy in the primary endpoint. However, in males it showed improvement of symptoms and functional parameters. BVE (using US) is a more optimal outcome measure than PVR in UAB.

100 项与 ASP-8302 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
膀胱功能不全	临床2期	英国	Astellas Pharma Europe Ltd.	2018-11-20
膀胱功能不全	临床2期	波兰	Astellas Pharma Europe Ltd.	2018-11-20
膀胱功能不全	临床2期	荷兰	Astellas Pharma Europe Ltd.	2018-11-20
膀胱功能不全	临床2期	德国	Astellas Pharma Europe Ltd.	2018-11-20
膀胱功能不全	临床2期	日本	Astellas Pharma Europe Ltd.	2018-11-20
膀胱功能不全	临床2期	斯洛伐克	Astellas Pharma Europe Ltd.	2018-11-20

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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


NCT03702777 (Pubmed \| Neurourol Urodyn)	临床2期	膀胱功能不全	135	ASP8302	(醖鹽膚顧糧餘壓鹹艱廠) = 願築襯鹹膚遞鬱網艱醖製窪廠艱衊製艱鑰遞鏇 (廠壓範顧繭蓋鏇鹽糧壓 ) 更多	不佳	2022-04-14
				Placebo	(醖鹽膚顧糧餘壓鹹艱廠) = 鹽顧襯壓壓構醖選製築製窪廠艱衊製艱鑰遞鏇 (廠壓範顧繭蓋鏇鹽糧壓 )