Delving into the Latest Updates on ASP-8302 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

M3 receptor

Mechanism

M3 receptor modulators(Muscarinic acetylcholine receptor M3 modulators)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Urinary Bladder, Underactive

Originator Organization

Astellas Pharma, Inc.

Active Organization-

Inactive Organization

Astellas Pharma Europe Ltd.

Astellas Pharma, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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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).

Start Date20 Nov 2018

Sponsor / Collaborator

Astellas Pharma Europe Ltd.

EUCTR2017-003693-13-PL / Not yet recruitingPhase 2

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

Start Date18 Oct 2018

Sponsor / Collaborator

Astellas Pharma Europe Ltd.

NCT03361540 / CompletedPhase 1

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.

Start Date14 Nov 2017

Sponsor / Collaborator

Astellas Pharma, Inc.

100 Clinical Results associated with ASP-8302

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100 Translational Medicine associated with ASP-8302

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100 Patents (Medical) associated with ASP-8302

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4

Literatures (Medical) associated with ASP-8302

01 Oct 2024·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

Author: 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.

01 Jul 2022·LUTS: Lower Urinary Tract SymptomsQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Jun 2022·Neurourology and UrodynamicsQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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 Deals associated with ASP-8302

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Urinary Bladder, Underactive	Phase 2	GB	Astellas Pharma Europe Ltd.	20 Nov 2018
Urinary Bladder, Underactive	Phase 2	PL	Astellas Pharma Europe Ltd.	20 Nov 2018
Urinary Bladder, Underactive	Phase 2	NL	Astellas Pharma Europe Ltd.	20 Nov 2018
Urinary Bladder, Underactive	Phase 2	DE	Astellas Pharma Europe Ltd.	20 Nov 2018
Urinary Bladder, Underactive	Phase 2	JP	Astellas Pharma Europe Ltd.	20 Nov 2018
Urinary Bladder, Underactive	Phase 2	SK	Astellas Pharma Europe Ltd.	20 Nov 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03702777 (Pubmed \| Neurourol Urodyn)	Phase 2	Urinary Bladder, Underactive	135	ASP8302	(rudnzzudfr) = kahqissugs jaruvbhiad (kwjfwjpcww ) View more	Negative	14 Apr 2022
				Placebo	(rudnzzudfr) = alhgmpbgue jaruvbhiad (kwjfwjpcww )