Objective: To investigate the efficacy and safety of ADS-5102 (amantadine HCl) extended release capsules 340 mg daily at bedtime for the treatment of levodopa-induced dyskinesia (LID).

Background: No medication is approved for LID in the US or EU. ADS-5102 is designed to improve the pharmacokinetic profile of immediate-release amantadine, with the aim of enhancing efficacy without compromising tolerability. ADS-5102 achieves maximal plasma amantadine concentrations in the early morning that are sustained throughout waking hours.

Methods: A double-blind, placebo-controlled study was conducted at 44 North American sites (NCT02136914) in Parkinson’s disease (PD) subjects with troublesome LID. Subjects were randomized to placebo (pbo) or ADS-5102. Treatment duration was 25 weeks (wks). The primary outcome measure was the change from baseline to wk 12 in the Unified Dyskinesia Rating Scale (UDysRS) total score. Key secondary measures were the change from baseline to wk 24 in the UDysRS total score, and the change from baseline to wks 12 and 24 in selected 24-hour (hr) PD diary states: ON time without troublesome dyskinesia (TrD), and OFF time. Other secondary measures included the MDS-Unified Parkinson’s disease Rating Scale (MDS-UPDRS).

Results: 126 subjects were randomized (63 in each arm). ADS-5102 significantly reduced LID as measured by change in the UDysRS total score over 12 wks vs pbo (p=0.0009). The reduction in LID was maintained through wk 24 (p=0.0008). Daily ON time without TrD increased by 2.7 hrs vs pbo over 12 wks (p<0.0001) and by 2.2 hrs over 24 wks (p=0.0007). Daily OFF time was reduced by 0.9 hrs and 0.8 hrs vs pbo over 12 wks (p=0.0171) and 24 wks (p=0.0406), respectively. ADS-5102 reduced motor complications as measured by change in the MDS-UPDRS, Part IV vs pbo over 12 wks and 24 wks (p=0.0005, p=0.0012, respectively). The most frequent adverse events (AE) were hallucinations, peripheral edema, dizziness, dry mouth, constipation, and falls. 21% of ADS-5102 subjects vs 7% of pbo subjects discontinued treatment due to AEs.

Conclusions: ADS-5102 was generally well tolerated and resulted in statistically significant, clinically meaningful, and durable improvement in LID, confirming results from an earlier Phase 2/3 study. A reduction in daily OFF time was also demonstrated.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ads-5102-amantadine-hcl-extended-release-capsules-reduced-levodopa-induced-dyskinesia-in-the-phase-3-ease-lid-study/