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

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.