A long-term study of istradefylline safety and efficacy in patients with Parkinson disease

Clin Neuropharmacol. Mar-Apr 2015;38(2):41-6. doi: 10.1097/WNF.0000000000000073.

Abstract

Objectives: Istradefylline is a selective adenosine A2A receptor antagonist. We evaluated the safety and efficacy of istradefylline administered once daily for 52 weeks in Parkinson disease (PD) patients experiencing wearing-off symptoms on levodopa therapy.

Methods: This was a phase 3, multicenter, open-label, long-term study in PD patients experiencing wearing-off who had previously completed a double-blind placebo-controlled clinical study of istradefylline in Japan. Istradefylline was administered for 52 weeks at a starting dosage of 20 mg/d, with or without dosage adjustment up to 40 mg/d. Safety was assessed using the incidence of treatment-emergent adverse events, and efficacy was assessed as the change in the daily off time.

Results: A total of 308 patients were included in this study. The most frequently reported treatment-emergent adverse events were nasopharyngitis (24.4%) and dyskinesia (21.4%). The mean change in the daily off time from day 1 was -0.65 hour in week 2, fluctuating between -0.71 and -0.04 hour until week 52 in patients who had previously taken placebo in the preceding double-blind study. The off time reduction from baseline of the double-blind study remained at similar levels between weeks 2 and 52 in patients who had previously taken istradefylline 20 and 40 mg/d in the preceding double-blind study.

Conclusions: This study showed that istradefylline treatment was well tolerated and produced a sustained reduction in off time in levodopa-treated PD patients over a 52-week period.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenosine A2 Receptor Antagonists / therapeutic use*
  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Purines / therapeutic use*
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Adenosine A2 Receptor Antagonists
  • Purines
  • istradefylline