Objective: Evaluate the effects of ADS-5102 (amantadine) extended release capsules on motor complications and functional outcomes among patients experiencing both troublesome dyskinesia and OFF (disruptive episodes) in phase 3 trials.

Background: Both OFF and dyskinesia can appear as Parkinson’s disease (PD) progresses, and both often disrupt daily function for people with PD. In two phase 3 trials (NCT02136914; NCT02274766), ADS-5102 provided significant improvement in both dyskinesia and OFF, and is the only FDA-approved medication for levodopa-induced dyskinesia in PD. OFF was a secondary outcome in these trials, however, many participants had substantial OFF time at baseline.

Method: This is a post-hoc analysis of ADS-5102 phase 3 trial participants who had ≥2.5 hours (h) daily OFF time at baseline (OFF subgroup), in line with common inclusion criteria for OFF treatment trials. Both study protocols required ≥1h/day of troublesome dyskinesia. Changes in dyskinesia, OFF, and functional outcomes were assessed by PD diaries, MDS-UPDRS (Parts II and IV), and UDysRS.

Results: The OFF subgroup included 101 (51%) of the 198 patients enrolled in the pivotal trials. Patients experienced a mean of 9 h/day in a disruptive motor state (4.4h OFF and 4.6h of troublesome dyskinesia), at baseline. The mean treatment difference at Week 12 was -1.2h (P<.001) OFF time and -2.0h (P<.001) troublesome dyskinesia. The mean number of daily disruptive episodes were reduced by 3.1 with ADS-5102 treatment, vs 1.4 for placebo (treatment difference, -1.7 episodes (P=.02)), and patients spent 4.2 fewer hours in a disruptive PD motor state each day with ADS-5102 vs 1.2h for placebo (treatment difference, -3.0h (P<.001)). The mean treatment differences at Week 12 for UDysRS and MDS-UPDRS (Parts II and IV) also improved (-10.5, -3.2, -2.6 points, respectively, P<.001 for all). Adverse events associated with ADS-5102 included hallucinations, peripheral edema, dry mouth, dizziness, fall, and constipation.

Conclusion: This post-hoc analysis of patients with troublesome dyskinesia and substantial OFF time demonstrated that ADS-5102 treatment significantly reduced both disruptive motor states (-3.0h total) and improved patient-reported motor function. ADS-5102 may help patients avoid the dilemma of sacrificing control of OFF to manage dyskinesia, and vice versa.

References: An abstract authored by Hauser et al., containing some of the data reported here, has been accepted for presentation at the 2020 annual meeting of the American Academy of Neurology in Toronto, ON.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/among-parkinsons-disease-patients-with-both-off-and-dyskinesia-ads-5102-amantadine-extended-release-reduces-disruptive-motor-episodes-and-improves-function-analysis-of-phase-3-trials/