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 PARTICIPANTSA 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 MEASURESThe 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 < .001). OFF time decreased by a mean (SE) of 0.6 (0.3) hours for ADS-5102 and increased by 0.3 (0.3) hours for placebo (treatment difference, -0.9 hours; 95% CI, -1.6 to -0.2; P = .02). Common adverse events for ADS-5102 vs placebo included visual hallucinations (15 [23.8%] vs 1 [1.7%]), peripheral edema (15 [23.8%] vs 0), and dizziness (14 [22.2%] vs 0). Adverse events led to treatment discontinuation for 13 patients receiving ADS-5102 (20.6%) vs 4 patients receiving placebo (6.9%).CONCLUSIONS AND RELEVANCE ADS-5102, 274 mg at bedtime, may be an effective treatment for LID. An additional benefit is reduced OFF time. To our knowledge, this is the first demonstration of an oral treatment reducing both LID and OFF time in patients with PD with dyskinesia.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02136914

Background: Many patients with Parkinson disease (PD) have excessive daytime sleepiness and numerous nocturnal sleep abnormalities. Objective: To determine the safety and efficacy of the controlled drug sodium oxybate in a multicenter, openlabel, polysomnographic study in subjects with PD and sleep disorders. Design, Setting, and Patients: Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleepdisordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off ("off") PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started sodium oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an off-medication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD). Results: We enrolled 38 subjects. At screening, 8 had sleep apnea (n=7) or depression (n=1). Twenty-seven of 30 subjects completed the study. Three dropped out owing to dizziness (n=3) and concurrent depression (n=1). The mean dose of sodium oxybate was 7.8 (1.7) g per night. The ESS score improved from 15.6 (4.2) to 9.0 (5.0) (PϽ.001); the Pittsburgh Sleep Quality Inventory score, from 10.9 (4.0) to 6.6 (3.9) (PϽ.001); and the Fatigue Severity Scale score, from 42.9 (13.2) to 36.3 (14.3) (P Ͻ.001). Mean slow-wave sleep time increased from 41.3 (33.2) to 78.0 (61.2) minutes (P =.005). Changes in off-medication UPDRS scores were not significant, from 28.4 (10.3) to 26.2 (9.6). Conclusion: Nocturnally administered sodium oxybate improved excessive daytime sleepiness and fatigue in PD.

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