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

Mov Disord. 2016 Jul;31(7):1049-54. doi: 10.1002/mds.26569. Epub 2016 Mar 15.

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.

Keywords: AQW051; Parkinson's disease; dyskinesias; levodopa (l-dopa); nicotinic acetylcholine receptor agonist (nAChR) α7.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

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

Substances

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