EASE LID 2: A 2-Year Open-Label Trial of Gocovri (Amantadine) Extended Release for Dyskinesia in Parkinson's Disease

J Parkinsons Dis. 2020;10(2):543-558. doi: 10.3233/JPD-191841.

Abstract

Background: Gocovri® (amantadine) extended release capsules are approved for the treatment of dyskinesia in patients with Parkinson's disease (PD) receiving levodopa-based therapy.

Objective: To evaluate the long-term safety, tolerability, and efficacy of Gocovri in patients with PD experiencing levodopa-induced dyskinesia.

Methods: In this 2-year open-label trial, patients completing double-blind Gocovri clinical trials or excluded from prior trials because of deep-brain stimulation (DBS) received Gocovri 274 mg once daily at bedtime. The primary objective was to evaluate long-term safety and tolerability. In addition, dyskinesia and OFF time were assessed using Part IV (Motor Complications) scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

Results: Among 223 enrolled patients (mean PD duration, 11.7 years; mean levodopa use, 9.3 years), 75.8% completed 1 year of treatment and 57.8% completed the trial, with a median treatment duration of 1.9 years. Common adverse events were fall (32.7%), hallucination (24.2%), peripheral edema (16.1%), constipation (13.5%), and urinary tract infection (10.3%); 31 patients (13.9%) discontinued because of adverse events considered related to study drug. At baseline, MDS-UPDRS Part IV scores were lower for patients continuing Gocovri (mean, 6.5 points) than for previous placebo (9.4) or DBS groups (10.5) but were similar for all groups by week 8 (6.3, 6.2, 6.4, respectively), and remained low for the duration of the trial (at week 100: 6.9, 7.3, 7.0, respectively).

Conclusions: In patients with PD, Gocovri showed long-term safety and tolerability consistent with double-blind trial findings, and durable reduction in motor complications (dyskinesia and OFF time).

Keywords: Amantadine; Gocovri; Levodopa; OFF; Parkinson’s disease; double-blind method; dyskinesias; extended-release preparations; hallucinations; humans; motor fluctuations; treatment.

Publication types

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

MeSH terms

  • Aged
  • Amantadine / administration & dosage
  • Amantadine / adverse effects
  • Amantadine / pharmacokinetics
  • Amantadine / pharmacology*
  • Delayed-Action Preparations
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / adverse effects
  • Dopamine Agents / pharmacokinetics
  • Dopamine Agents / pharmacology*
  • Dyskinesia, Drug-Induced / drug therapy*
  • Female
  • Humans
  • Levodopa / adverse effects*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Parkinson Disease / drug therapy*

Substances

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