A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease.

Introduction: This study examined the safety and pharmacodynamic effects of selective muscarinic M 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.