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.
Alzheimers Dement (N Y)
; 8(1): e12273, 2022.
Article
em En
| MEDLINE
| ID: mdl-35229025
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, 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.
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Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article