Safety and Efficacy of Istradefylline in Parkinson's Disease Patients With and Without Preexisting Dyskinesia: Pooled Analysis of 8 Randomized Controlled Trials.

Objective: To evaluate the efficacy of istradefylline in Parkinson's disease patients experiencing motor fluctuations with and without dyskinesia and characterize potential predictors for treatment-emergent dyskinesia with istradefylline.

Methods: Pooled analysis of 8 phase 2b/3 trials of istradefylline (20 or 40 mg/day) versus placebo.

Results: Data from 2,719 patients, 56% of whom presented with baseline dyskinesia, were analyzed post hoc. The presence of baseline dyskinesia did not affect the mean decrease in "OFF" time with dyskinesia, increase in "ON" time without troublesome dyskinesia, or improvement in the Unified Parkinson's Disease Rating Scale motor score associated with istradefylline treatment. Dyskinesia was reported in 17% of patients receiving istradefylline, with higher rates for women (21%), patients with a BMI <18.5 kg/m2 (22%), and patients receiving catechol-o-methyltransferase inhibitors plus dopamine agonists (22%) and monoamine oxidase B inhibitors (25%).

Conclusion: Istradefylline treatment resulted in greater reductions in total "OFF" hours/day and increases in "ON" time without troublesome dyskinesia than did placebo, regardless of the presence or absence of preexisting dyskinesia.