ASP8302 / Astellas - LARVOL DELTA

A Study of ASP8302 in Participants With Underactive Bladder (clinicaltrials.gov) - P2 | N=135 | Completed | Sponsor: Astellas Pharma Europe B.V. | Phase classification: P2a ➔ P2

Phase classification • Urology

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024. (PubMed, Neurourol Urodyn) - "Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive."

Journal • Review • Urology • GRP-10

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor-Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development."

Journal • PK/PD data

Muscarinic-3-receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial. (PubMed, Neurourol Urodyn) - "ASP8302 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."

Clinical • Journal • Overactive Bladder • Urinary Incontinence • Urology

Muscarinic M positive allosteric modulator ASP8302 enhances bladder contraction and improves voiding dysfunction in rats. (PubMed, Low Urin Tract Symptoms) - "Our 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."

Journal • Preclinical • Anesthesia

Potentiation of muscarinic M receptor activation through a new allosteric site with a nove l positive allosteric modulator ASP8302. (PubMed, J Pharmacol Exp Ther) - "In cells expressing human M and M receptors, ASP8302 shifted the concentration-response curve (CRC) for carbachol to the lower concentrations with no significant effects on other subtypes. Significance Statement The significance of this study is that the novel M receptor positive allosteric modulator ASP8302 enhances the activation of human M receptor by interacting with a residue distinct from the reported allosteric sites. The finding of Thr as a novel amino acid involved in the allosteric modulation of M receptors provides significant insight into further research of the mechanism of allosteric modulation of M and other muscarinic receptors."

Journal • Immunology

A Study of ASP8302 in Participants With Underactive Bladder (clinicaltrials.gov) - P2a; N=135; Completed; Sponsor: Astellas Pharma Europe B.V.; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of ASP8302 in Participants With Underactive Bladder (clinicaltrials.gov) - P2a; N=135; Active, not recruiting; Sponsor: Astellas Pharma Europe B.V.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of ASP8302 in Participants With Underactive Bladder (clinicaltrials.gov) - P2a; N=130; Recruiting; Sponsor: Astellas Pharma Europe B.V.; Trial completion date: Nov 2019 ➔ Jun 2020; Trial primary completion date: Nov 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date