Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)

Mov Disord. 2015 May;30(6):788-95. doi: 10.1002/mds.26159. Epub 2015 Feb 4.

Abstract

ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P = 0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P = 0.004), 340 mg (P = 0.008) and 420 mg (P = 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.

Keywords: Parkinson's disease; amantadine; clinical trial; levodopa-induced dyskinesia; randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amantadine / administration & dosage*
  • Amantadine / therapeutic use*
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dyskinesia, Drug-Induced / drug therapy*
  • Dyskinesia, Drug-Induced / physiopathology
  • Female
  • Humans
  • Levodopa / adverse effects*
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Levodopa
  • Amantadine