Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson's disease: A single-arm, open-label, prospective, multicenter study

Expert Opin Pharmacother. 2019 Aug;20(11):1405-1411. doi: 10.1080/14656566.2019.1614167. Epub 2019 May 28.

Abstract

Background: Gait disorders are common in Parkinson's disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A2A receptor antagonist with benefits for motor complications associated with Parkinson's disease. Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson's disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed. Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4-12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients. Conclusions: Istradefylline improved gait disorders in Parkinson's disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified. Trial registration: UMIN-CTR (UMIN000020288).

Keywords: Adenosine A receptor antagonist; Parkinson’s disease; freezing of gait; gait disorders; istradefylline.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adenosine A2 Receptor Antagonists / adverse effects
  • Adenosine A2 Receptor Antagonists / therapeutic use*
  • Administration, Oral
  • Aged
  • Drug Administration Schedule
  • Dyskinesias / etiology
  • Female
  • Gait / physiology
  • Gait Disorders, Neurologic / complications
  • Gait Disorders, Neurologic / drug therapy
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Prospective Studies
  • Purines / adverse effects
  • Purines / therapeutic use*
  • Quality of Life
  • Treatment Outcome

Substances

  • Adenosine A2 Receptor Antagonists
  • Purines
  • istradefylline