Istradefylline as monotherapy for Parkinson disease: Results of the 6002-US-051 trial

Abstract Objective 6002-US-051 was a 12-week, double-blind study evaluating the safety and efficacy of istradefylline, a selective A2A 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.