A 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.

ABSTRACT:

Introduction

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

SUBMITTER: Nathan PJ 

PROVIDER: S-EPMC8864442 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature