{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:53:49Z","timestamp":1789610029004,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3\u2010PAM), in patients with underactive bladder (UAB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, double\u2010blind, placebo\u2010controlled multicenter study was performed in adult male\/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR]\u2009&gt;\u2009100\u2009ml) without significant bladder outlet obstruction and\/or overactive bladder. Subjects were randomized (1:1) to receive 4\u2010week oral once\u2010daily administration of 100\u2009mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVR<jats:sub>C2<\/jats:sub>). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressure\u2010flow studies were performed in a subgroup.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred and thirty\u2010five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVR<jats:sub>C2<\/jats:sub> was \u221240.0\u2009ml (ASP8302) versus \u221235.0\u2009ml (placebo) and the difference between groups was \u22125.0\u2009ml (<jats:italic>p<\/jats:italic>\u2009=\u20090.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (<jats:italic>Q<\/jats:italic><jats:sub>max<\/jats:sub>) and detrusor pressure at <jats:italic>Q<\/jats:italic><jats:sub>max<\/jats:sub> (<jats:italic>P<\/jats:italic><jats:sub>det.Qmax<\/jats:sub>) increased (mean difference in change ASP8302 vs. placebo: 3.8\u2009ml\/s, <jats:italic>p<\/jats:italic>\u2009=\u20090.031 and 12.7\u2009cm\u2009H<jats:sub>2<\/jats:sub>O, <jats:italic>p<\/jats:italic>\u2009=\u20090.034, respectively). Urinary incontinence episodes\/24\u2009h decreased in males with preexisting incontinence (mean difference: \u22120.35; <jats:italic>p<\/jats:italic>\u2009=\u20090.028). 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]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24931","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T08:49:46Z","timestamp":1649926186000},"page":"1139-1148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Muscarinic\u20103\u2010receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-9332","authenticated-orcid":false,"given":"Jan Willem Olivier","family":"van Till","sequence":"first","affiliation":[{"name":"Medical and Development Astellas Pharma Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Arita","sequence":"additional","affiliation":[{"name":"Medical and Development Astellas Pharma Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kuroishi","sequence":"additional","affiliation":[{"name":"Medical and Development Astellas Pharma Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Croy","sequence":"additional","affiliation":[{"name":"Medical and Development Astellas Pharma Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Oelke","sequence":"additional","affiliation":[{"name":"Department of Urology, Paediatric Urology and Uro\u2010Oncology St. Antonius Hospital  Gronau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gommert A.","family":"van Koeveringe","sequence":"additional","affiliation":[{"name":"Department of Urology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Chapple","sequence":"additional","affiliation":[{"name":"Department of Urology The Royal Hallamshire Hospital  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Urology Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2776-2200","authenticated-orcid":false,"given":"Paul","family":"Abrams","sequence":"additional","affiliation":[{"name":"Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital  Bristol 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