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Original Investigation
Clinical Trial
August 2017

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

Author Affiliations
  • 1Department of Neurology, University of Kansas Medical Center, Kansas City
  • 2Department of Neurology, University California–San Francisco
  • 3Parkinson’s Disease Research, Education and Clinic Center, San Francisco Veterans Affairs Medical Center, San Francisco, California
  • 4Health Byrd Parkinson’s Disease and Movement Disorders Center of Excellence, University of South Florida, Tampa
  • 5Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida
  • 6Wisconsin Institute for Neurologic and Sleep Disorders, Milwaukee
  • 7The Parkinson’s and Movement Disorder Institute, Fountain Valley, California
  • 8Booth Gardner Parkinson’s Care Center, Evergreen Health, Kirkland, Washington
  • 9Raleigh Neurology Associates, Raleigh, North Carolina
  • 10Adamas Pharmaceuticals Inc, Emeryville, California
JAMA Neurol. 2017;74(8):941-949. doi:10.1001/jamaneurol.2017.0943
Key Points

Question  Are 274-mg ADS-5102 (amantadine) extended-release capsules safe and effective for the treatment of levodopa-induced dyskinesia in Parkinson disease?

Findings  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%).

Meaning  ADS-5102 may be an effective treatment for levodopa-induced dyskinesia.

Abstract

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 < .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

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