Are 274-mg ADS-5102 (amantadine) extended-release capsules safe and effective for the treatment of levodopa-induced dyskinesia in Parkinson disease?
In this randomized clinical trial, ADS-5102 was associated with a significantly greater reduction in the duration, severity, and impact of dyskinesia at 12 weeks compared with placebo, as measured by the least-squares mean change in the Unified Dyskinesia Rating Scale score (treatment difference, –7.9); this reduction in the duration, severity, and impact of dyskinesia was maintained through week 24 (treatment difference, –9.3). Adverse events led to treatment discontinuation for 13 of 63 patients receiving ADS-5102 (20.6%) vs 4 of 58 patients receiving placebo (6.9%).
ADS-5102 may be an effective treatment for levodopa-induced dyskinesia.
Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) is an unmet need.
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.
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).
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.
clinicaltrials.gov Identifier: NCT02136914
Pahwa R, Tanner CM, Hauser RA, Isaacson SH, Nausieda PA, Truong DD, Agarwal P, Hull KL, Lyons KE, Johnson R, Stempien MJ. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study)A Randomized Clinical Trial. JAMA Neurol. 2017;74(8):941–949. doi:10.1001/jamaneurol.2017.0943