A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia.

Abstract

BACKGROUND:

This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia.

METHODS:

Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics.

RESULTS:

In total, 67 patients completed the study. AQW051-treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls.

CONCLUSIONS:

AQW051 did not significantly reduce dyskinesia or parkinsonian severity. © 2016 International Parkinson and Movement Disorder Society.

• Authors: Claudia Trenkwalder, Daniela Berg, Olivier Rascol, Karla Eggert, Andres Ceballos-Baumann, Jean-Christophe Corvol, Alexander Storch, Lin Zhang, Jean-Philippe Azulay, Emmanuel Broussolle, Luc Defebvre, Christian Geny, Michal Gostkowski, Fabrizio Stocchi, Christine Tranchant, Pascal Derkinderen, Franck Durif, Alberto J Espay, Andrew Feigin, Jean-Luc Houeto, Johannes Schwarz, Thérèse Di Paolo, Dominik Feuerbach, Hans-Ulrich Hockey, Judith Jaeger, Annamaria Jakab, Donald Johns, Gurutz Linazasoro, Paul Maruff, Izabela Rozenberg, Judit Sovago, Markus Weiss, Baltazar Gomez-Mancilla
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 31 Issue 7 Pg. 1049-54 (07 2016) ISSN: 1531-8257 [Electronic] United States
• PMID: 26990766 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 International Parkinson and Movement Disorder Society.

Chemical References

• 3-(6-p-tolylpyridin-3-yloxy)-1-azabicyclo(2.2.2)octane
• Antiparkinson Agents
• Azabicyclo Compounds
• Dopamine Agents
• Pyridines
• alpha7 Nicotinic Acetylcholine Receptor
• Levodopa

Topics

• Aged
• Antiparkinson Agents (administration & dosage, adverse effects, pharmacology)
• Azabicyclo Compounds (administration & dosage, adverse effects, pharmacology)
• Dopamine Agents (adverse effects)
• Double-Blind Method
• Dyskinesia, Drug-Induced (drug therapy, etiology)
• Female
• Humans
• Levodopa (adverse effects)
• Male
• Middle Aged
• Outcome Assessment, Health Care
• Parkinson Disease (drug therapy)
• Pyridines (administration & dosage, adverse effects, pharmacology)
• alpha7 Nicotinic Acetylcholine Receptor (agonists)