> Detailanzeige

Nathan, Pradeep J.; Millais, S. Babli; Godwood, Alex; Dewit, Odile; Cross, David M.; Liptrot, Janet; Ruparelia, Bharat; Jones, Stephen Paul; Bakker, Geor; Maruff, Paul T.; Light, Gregory A.; Brown, Alastair J.H.; Weir, Malcolm Peter; Congreve, Miles; Tasker, Tim

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

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: 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
  • Beteiligte: Nathan, Pradeep J.; Millais, S. Babli; Godwood, Alex; Dewit, Odile; Cross, David M.; Liptrot, Janet; Ruparelia, Bharat; Jones, Stephen Paul; Bakker, Geor; Maruff, Paul T.; Light, Gregory A.; Brown, Alastair J.H.; Weir, Malcolm Peter; Congreve, Miles; Tasker, Tim
  • Erschienen: Wiley, 2022
  • Erschienen in: Alzheimer's & Dementia: Translational Research & Clinical Interventions
  • Sprache: Englisch
  • DOI: 10.1002/trc2.12273
  • ISSN: 2352-8737
  • Schlagwörter: Psychiatry and Mental health ; Neurology (clinical)
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>This study examined the safety and pharmacodynamic effects of selective muscarinic M<jats:sub>1</jats:sub> receptor orthosteric agonist HTL0018318 in 60 patients with mild‐to‐moderate Alzheimer's disease (AD) on background donepezil 10 mg/day.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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.</jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang