Movement Disorders

Extended Release Amantadine Effective for Reducing Dyskinesia in Parkinson Disease

Sunali Wadehra, MD
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Although relatively rare in occurrence, movement disorders are strongly associated with APS. Chorea is the most frequently observed, with a prevalence ranging from 1.3% to 4.5%.4 Other movement disorders can also occur, including ballismus, dyskinesia, cerebellar ataxia, and parkinsonism. The majority of patients who develop APL-related chorea are young and female, and have primary APS or APS secondary to SLE. The use of oral contraception or pregnancy may trigger chorea in some patients,4,5 the symptoms of which may evolve slowly over weeks or longer, usually isolated to 1 side of the body. Often there is only 1 attack, which may precede other neurologic symptoms.5 Chorea associated with APS is generally treated symptomatically with dopamine receptor agonists and immunosuppressive therapies such as corticosteroids and cyclophosphamide.4

Although relatively rare in occurrence, movement disorders are strongly associated with APS. Chorea is the most frequently observed, with a prevalence ranging from 1.3% to 4.5%.4 Other movement disorders can also occur, including ballismus, dyskinesia, cerebellar ataxia, and parkinsonism.

The majority of patients who develop APL-related chorea are young and female, and have primary APS or APS secondary to SLE. The use of oral contraception or pregnancy may trigger chorea in some patients,4,5 the symptoms of which may evolve slowly over weeks or longer, usually isolated to 1 side of the body. Often there is only 1 attack, which may precede other neurologic symptoms.5 Chorea associated with APS is generally treated symptomatically with dopamine receptor agonists and immunosuppressive therapies such as corticosteroids and cyclophosphamide.4

ADS-5102 is a promising treatment option: if taken once daily at night, it achieves highest plasma drug concentrations throughout the day when symptoms are most bothersome.

ADS-5102 (high-dose amantadine ER formulation) improves dyskinesia associated with levodopa use in Parkinson disease (PD) and decreases the total time per day during which levodopa has worn off, according to a study published in CNS Drugs.

Amantadine, a glutamate antagonist, alleviates side effects of dyskinesia from levodopa use. ADS-5102 is a promising treatment option: if taken once daily at night, it achieves highest plasma drug concentrations throughout the day when symptoms are most bothersome.

Investigators conducted a pooled analysis of 2 randomized, double-blind, placebo-controlled, phase 3 trials of ADS-5102, EASE LID and EASE LID 3. Both trials were identical in design; however, ADS-5102 treatment duration in EASE LID was 25 weeks vs 13 weeks for EASE LID 3. Only common assessment time points were analyzed, including baseline and weeks 2, 8, and 12. 

Patients were randomly assigned in a 1:1 ratio to take ADS-5102 (n=100) vs placebo (n=96) once daily at night. ADS-5102 was administered at 274 mg dosages, except during the first and final weeks of the study, in which 137 mg dosages were administered. Unified Dyskinesia Rating Scale (UDysRS), was used per visit. Also, patients kept a home diary 2 days before and after visits, assessing their clinical status every half-hour. 

The primary end point was defined as a change from baseline to week 12 in each patient’s UDysRS total score. The least squares (LS) mean change in the ADS-5102 vs placebo group was −17.7 (standard error [SE] 1.3) vs −7.6 (1.3) points, respectively (−10.1 points; 95% CI, −13.8 to −6.5; P <.0001). The relative treatment difference between groups was 27.3% (P <.0001). 

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Secondary end points included patients’ diary-based assessments. The LS mean change in time levodopa had worn off was −0.59 (0.21) vs. +0.41 (0.20) h/day, a difference of −1.00 h/day (95% CI, −1.57 to −0.44; P =.0006). 

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Common adverse events in patients in the ADS-5102 group included hallucinations, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. 

Results of this study suggest ADS-5102 may be a viable adjunct to levodopa for the management of dyskinesia in patients with PD.   

Disclosures: Funding for this study was provided by Adamas Pharmaceuticals, Inc.  Several authors declare affiliations with Adamas.  

Reference

Elmer LW, Juncos JL, Singer C, et al.  Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson’s disease [published online March 12, 2018]. CNS Drugs. doi:10.1007/s40263-018-0498-4

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