Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial.
OBJECTIVE
6002-US-051 was a 12-week, double-blind study evaluating the safety and efficacy of istradefylline, a selective A(2A) adenosine receptor antagonist, as monotherapy in patients with Parkinson's disease (PD).


METHODS
Patients with Hoehn-Yahr stages 1-2.5 who had not received dopaminergic drugs in the past 30 days or levodopa for >30 days at anytime were randomized to 40 mg/day istradefylline or placebo. The primary efficacy outcome was the change from Baseline to Endpoint in the Unified Parkinson's Disease Rating Scale (UPDRS) Subscale III score. Safety was assessed by physical examination, laboratory tests, electrocardiograms, and adverse event monitoring.


RESULTS
176 patients comprised the intent-to-treat population. Although istradefylline showed numerically greater improvements in UPDRS Subscale III at each time point and reached statistical significance at Week 2 (LS mean difference = -1.47), it did not show statistically significant improvement from placebo for the primary endpoint (least square [LS] mean difference = -1.11). Similar proportions of patients in each group experienced treatment-emergent adverse events (63% istradefylline, 65% placebo).


CONCLUSIONS
Istradefylline, as monotherapy in patients with PD, is safe and well tolerated. However, efficacy in improving motor symptoms in early PD was not statistically demonstrated by this study.
Fernandez
H H
HH
Department of Neurology, University of Florida Movement Disorders Center, PO Box 100236, 100 South Newell Dr., L3-100, Gainesville, FL 32610-0236, USA. fernandez@neurology.ufl.edu <fernandez@neurology.ufl.edu>
Greeley
D R
DR
Zweig
R M
RM
Wojcieszek
J
J
Mori
A
A
Sussman
N M
NM
D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D011687:Purines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014481:United States
D000978:Antiparkinson Agents; D011687:Purines; C111599:istradefylline