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dc.contributor.authorNathan, Pradeep J
dc.contributor.authorMillais, S Babli
dc.contributor.authorGodwood, Alex
dc.contributor.authorDewit, Odile
dc.contributor.authorCross, David M
dc.contributor.authorLiptrot, Janet
dc.contributor.authorRuparelia, Bharat
dc.contributor.authorJones, Stephen Paul
dc.contributor.authorBakker, Geor
dc.contributor.authorMaruff, Paul T
dc.contributor.authorLight, Gregory A
dc.contributor.authorBrown, Alastair JH
dc.contributor.authorWeir, Malcolm Peter
dc.contributor.authorCongreve, Miles
dc.contributor.authorTasker, Tim
dc.date.accessioned2022-02-23T11:00:07Z
dc.date.available2022-02-23T11:00:07Z
dc.date.issued2022
dc.date.submitted2021-06-02
dc.identifier.issn2352-8737
dc.identifier.othertrc212273
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334362
dc.descriptionFunder: Allergan Incorporated (now AbbVie)
dc.description.abstractINTRODUCTION: This study examined the safety and pharmacodynamic effects of selective muscarinic M1 receptor orthosteric agonist HTL0018318 in 60 patients with mild-to-moderate Alzheimer's disease (AD) on background donepezil 10 mg/day. METHODS: A randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition. RESULTS: Treatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil.
dc.languageen
dc.publisherWiley
dc.subjectRESEARCH ARTICLE
dc.subjectRESEARCH ARTICLES
dc.subjectAlzheimer's disease
dc.subjectattention
dc.subjectcholinergic
dc.subjectclinical trial
dc.subjectcognition
dc.subjectCogstate neuropsychological test battery
dc.subjectelectrophysiology
dc.subjectevent related potential
dc.subjectHTL0018318
dc.subjectmemory
dc.subjectmuscarinic M1 receptor
dc.subjectpharmacodynamic
dc.subjectsafety
dc.subjectsymptomatic
dc.subjecttolerability
dc.titleA phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M1 receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease.
dc.typeArticle
dc.date.updated2022-02-23T11:00:07Z
prism.issueIdentifier1
prism.publicationNameAlzheimers Dement (N Y)
prism.volume8
dc.identifier.doi10.17863/CAM.81776
dcterms.dateAccepted2022-01-25
rioxxterms.versionofrecord10.1002/trc2.12273
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.contributor.orcidNathan, Pradeep J [0000-0003-0943-5329]
dc.contributor.orcidMillais, S Babli [0000-0002-1824-3444]
dc.identifier.eissn2352-8737
cam.issuedOnline2022-02-23


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