Extended-Release Amantadine Reduces Levodopa-Induced Dyskinesia in Parkinson's Disease

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Dyskinesia is a troublesome adverse effect of Parkinson’s disease treatment that can have an impact on motor function and overall quality of life.
Dyskinesia is a troublesome adverse effect of Parkinson’s disease treatment that can have an impact on motor function and overall quality of life.

A study recently published in JAMA Neurology found that daily dosing of amantadine was effective in controlling levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD).1 Bedtime administration of ADS-5102, a developmental formulation of amantadine in an extended-release capsule, reduced the severity and duration of LID, as well as the impact of LID on daily function.

Investigators from multiple neurological centers specializing in PD collaborated on the phase 3, randomized, double-blind, placebo-controlled clinical trial ADS-5102 Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia (EASE LID) conducted across 44 sites in the United States from May 2014 to July 2015. A total of 121 patients (51 women, 70 men; mean age, 64.7) were randomly assigned to receive either placebo or ADS-5102 at doses of 137 mg during week 1 and week 24 and 274 mg during weeks 2 through 23.

A significant reduction in Unified Dyskinesia Rating Scale (UDysRS) score was seen at week 12 of –15.9 (least squares mean (SE) change of 1.6) for ADS-5102 (n=63) compared with  –8.0 (SE 1.6) for placebo (n=58) for a treatment difference of –7.9 (95% CI, –12.5 to –3.3; P <.001), and also for the secondary outcome at week 24 (reductions of –6.3 (1.9) and –15.6 (1.9), respectively, for an SE change of –9.3 (95% CI, –14.7 to –4.0; P <.001). The treatment effect was consistent across all subgroups (sex, age, body mass index, renal clearance, and dyskinesia severity).

Secondary outcomes also included changes in ON and OFF times, assessed at 12 and 24 weeks using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Clinician's Global Impression of Change (CGIC) scores, and patient diaries. Mean ON time without troublesome dyskinesia according to PD diaries was improved by 3.6 (0.4, SD) hours in the treatment group compared with 0.9 (0.4) hours for placebo and at 24 weeks, 3.6 (0.4) vs 1.4 (0.5) hours, respectively. OFF times improved by –0.6 (0.3) hours in the treatment group vs 0.3 (0.3) hours on placebo at 12 weeks, and by –0.6 (0.3) vs 0.2 (0.3) hours at 24 weeks. The improvement in ON times was attributed to decreases in OFF and ON times with troublesome dyskinesia.

Improvements in overall symptoms of PD including dyskinesia were measured by increased CGIC scores in 81% (51 of 63) of patients taking ADS-5102 compared with 36.2% (21 of 58) taking placebo(P <.001). In addition, the investigators observed an overall lack of differences between ADS-5102 and placebo observed in the ON state in MDS-UPDRS scores at weeks 12 and 24, indicating that ADS-5102 did not worsen PD motor function.

The combined evidence from this trial suggests that ADS-5102 274 mg at bedtime is effective in the treatment of LID, with the additional benefit of reduced OFF time in patients with PD and dyskinesia.

Reference

Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID Study) a randomized clinical trial [published online June 12, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2017.0943

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