title: Istradefylline for Parkinson's disease patients experiencing motor fluctuations: results of the KW-6002-US-018 study.
abstract: BACKGROUND
  Istradefylline (KW-6002) is a selective adenosine A(2A) receptor antagonist investigated as adjunctive therapy to levodopa in PD patients with motor response complications. In Phase 2b/3 studies, Istradefylline reduced OFF time without worsening troublesome dyskinesia and was well tolerated.
  
  
  METHODS
  A randomized, 12-week, double-blind, placebo-controlled parallel-group study evaluated the efficacy of 10, 20, and 40 mg/day of Istradefylline in patients on levodopa therapy with motor response complications. The primary outcome measure was change from baseline to endpoint in the percentage of awake time/day spent in the OFF state as determined by patient diary.
  
  
  RESULTS
  Six hundred and ten patients were randomized. Five hundred and eighty four patients were included in the Intent-to-treat (ITT) group-146 placebo patients and 149 in the 10 mg, 144 in the 20, and 145 patients in the 40 mg Istradefylline groups. Baseline demographics were similar between groups. Treatment cohorts had been diagnosed an average of 9 years diagnosis and 3.6 years from the onset of motor fluctuations; at baseline they had an average of 6.7 h of OFF time and an average UPDRS motor score of 22 when ON. At endpoint, the amount and percentage of OFF time did not differ between Istradefylline and placebo, however a dose-ordering response was observed. Changes from baseline in the UPDRS motor score in the on state for the 40 mg were modest but significant compared to placebo (2.9 vs. 0.8; p < 0.05).
  
  
  CONCLUSIONS
  Although Istradefylline did not impact OFF time duration, it significantly improved motor score at 40 mg/day.
authors: Clinique Sainte-Anne-Laval University, 1248, Chemin Sainte-Foy, Suite # 304, Quebec, Canada. psa@riq.qc.ca
authors: Emmanuelle
authors: E
authors: Pourcher
authors: Hubert H
authors: HH
authors: Fernandez
authors: Mark
authors: M
authors: Stacy
authors: Akihisa
authors: A
authors: Mori
authors: Rocco
authors: R
authors: Ballerini
authors: Philip
authors: P
authors: Chaikin
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011687:Purines / Q000627:therapeutic use*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D011687:Purines; C111599:istradefylline