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

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 levodopainduced 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).

Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia

“…The drug underwent a final 2-year open-label trial in 223 PD patients with LID and showed long-term safety, tolerability, and efficacy on dyskinesia and OFF time. 107 However, the drug is not available outside the US.…”

Amantadine ER (Gocovri®) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson's Disease

“…In the longer EASE LID study, treatment benefits in increasing ON time without troublesome dyskinesia, and reducing OFF time, time spent ON with troublesome dyskinesia and with dyskinesia (troublesome + non-troublesome) were maintained and were all significantly different than placebo (all p < 0.05) among those patients who completed the entire 24 weeks of treatment (before the study was prematurely stopped to allow regulatory filing) ( 14 ). Recent analyses of the open-label EASE-LID 2 study further showed maintenance of benefits in terms of reducing ON time with dyskinesia and OFF time (as assessed by the MDS-UPDRS Part IV) over 2 years ( 28 ). Finally, while patients in the trial had to have peak-dose dyskinesia, other forms of dyskinesia were not excluded, and combinations of choreic and dystonic movements, peak-dose and end-of-dose dyskinesias often occur in the same patient.…”

Development, Efficacy and Safety of Once-daily, Bedtime, Extended-release Amantadine (Gocovri®) to Treat Dyskinesia and OFF Time in Parkinson’s Disease

“…The amantadine ER(Go) development programme included non-clinical toxicology studies to meet current standards, and pharmacokinetic studies, in addition to the following clinical studies: the phase II/III EASED study (Extended release Amantadine Safety and Efficacy study in levodopainduced Dyskinesia), which was a dose-finding study; 59 the pivotal EASE LID and EASE LID 3 studies (Extended release Amantadine Safety and Efficacy studies in Levodopa-Induced Dyskinesia); 40,41 and the 2-year, open-label EASE LID 2 study. 60 An overview of these studies is included in Table 1.…”