Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson’s Disease

Abstract

Background: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson’s disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRI TM ) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day. Objective: In this study, we present pooled results from two randomized, double-blind, placebo-controlled, phase III ADS-5102 trials. Patients and Methods: The two studies in PD patients with dyskinesia shared design and eligibility criteria, differing only in treatment duration. Results from common assessment time points were pooled. Results: At 12 weeks, the least squares (LS) mean change in total score on the Unified Dyskinesia Rating Scale among 100 patients randomized to ADS-5102 and 96 patients randomized to placebo was − 17.7 (standard error [SE] 1.3) vs. − 7.6 (1.3) points, respectively (− 10.1 points, 95% confidence interval [CI] − 13.8, − 6.5; p < 0.0001). The relative treatment difference between groups was 27.3% (p < 0.0001). At 12 weeks, the LS mean change in OFF time was − 0.59 (0.21) vs. +0.41 (0.20) h/day, a difference of − 1.00 h/day (95% CI − 1.57, − 0.44; p = 0.0006). For both efficacy measures, a significant difference from placebo was attained by two weeks, the first post-baseline assessment, and was maintained throughout 12 weeks. In the pooled ADS-5102 group, the most common adverse events were hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. Conclusions: These analyses provide further evidence supporting ADS-5102 as an adjunct to levodopa for treating both dyskinesia and OFF time in PD patients with dyskinesia. Clinicaltrials.gov identifier: NCT02136914 and NCT02274766.