biostudies-literatureUnknown8(1)Nathan PJ<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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-doseAlzheimer's & dementia (New York, N. Y.)e12273https://www.ebi.ac.uk/biostudies/studies/S-EPMC8864442biostudies-literatureA 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.PMC8864442Bakker GCross DMCongreve MJones SPNathan PJGodwood ARuparelia BTasker TMillais SBMaruff PTDewit OLiptrot JBrown AJHLight GAWeir MPfalseA 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.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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-dose2022-01-01T00:00:00Z20222026-06-18T06:00:41.256Z2025-04-05T21:04:11.366ZS-EPMC88644423522902510.1002/trc2.12273