ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial

IMPORTANCE: Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) is an unmet need. OBJECTIVE: To evaluate the efficacy and safety of ADS-5102 (amantadine) extended-release 274-mg capsules for treatment of LID in patients with PD. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled clinical trial was conducted between May 7, 2014, and July 22, 2015, at 44 North American sites among patients with PD treated with levodopa who experienced at least 1 hour of troublesome dyskinesia per day with at least mild functional impact. INTERVENTIONS: Patients were randomized to receive placebo or 274 mg of ADS-5102 administered orally at bedtime for up to 25 weeks. MAIN OUTCOMES AND MEASURES: The primary efficacy analysis was the change from baseline to week 12 in the Unified Dyskinesia Rating Scale total score for ADS-5102 vs placebo in the modified intent-to-treat population. OFF time (amount of time the PD medication is not controlling motor symptoms) was a key secondary end point. Safety analyses included all patients who received the study drug (ADS-5102 or placebo). RESULTS: A total of 189 patients were screened, and 126 were randomized; the modified intent-to-treat population included 121 patients (51 women and 70 men; mean [SD] age, 64.7 [9.1] years). At week 12, the least-squares mean (SE) change in the Unified Dyskinesia Rating Scale score was –15.9 (1.6) for ADS-5102 (n = 63) and –8.0 (1.6) for placebo (n = 58) (treatment difference, –7.9; 95% CI, –12.5 to –3.3; P