Gocovri Reduces Disruptive Motor Episodes and Improves Function in Parkinson’s Disease Patients With OFF Episodes and Dyskinesia: Analysis of Phase 3 Trial Data
Robert Hauser1, Dustin Chernick2, Andrea Formella2
1University of South Florida, 2Adamas Pharmaceuticals, Inc.
Objective:
Evaluate the ability of Gocovri® (amantadine) extended release capsules to reduce disruptive motor episodes (OFF and troublesome dyskinesia) and improve patient function.
Background:
OFF episodes and dyskinesia can emerge with Parkinson’s disease (PD) progression, and both can disrupt and impair daily function. Gocovri is the only FDA-approved medication for levodopa-induced dyskinesia in PD, and was studied in two phase 3 trials (NCT02136914; NCT02274766). Gocovri has not been studied in a trial designed for OFF as a primary outcome; however, many patients in the trials had substantial OFF time at baseline. Treatment trials for OFF generally require ~2.5 hours of OFF time/day for enrollment. Therefore, we analyzed patients in Gocovri trials who were experiencing this amount of OFF time upon enrollment.
Design/Methods:
Gocovri trial participants with ≥2.5 hours baseline OFF time were analyzed. By enrollment criteria, patients also had ≥2 half-hour periods of troublesome dyskinesia per day. Gocovri vs. placebo treatment differences at week 12 endpoint were determined for PD diary, MDS-UPDRS Parts II and IV, and UDysRS data using MMRM.
Results:
Of 198 enrolled patients, 101 (51%) composed the OFF subgroup. At baseline, mean OFF time was 4.4 hours and ON time with troublesome dyskinesia was 4.6 hours. At week 12, placebo-adjusted change in OFF time was -1.2 h (P<.001) and troublesome dyskinesia was –2.0 h (P<.001). Gocovri resulted in 1.7 fewer disruptive episodes (P=.02) and 3.0 fewer hours/day spent in disruptive PD motor states (P<.001). Placebo-adjusted treatment differences in UDysRS, MDS-UPDRS Part II and Part IV scores also favored Gocovri (-10.5, -3.2, -2.6 points, P<.001 for all). Gocovri-related AEs included hallucinations, peripheral edema, dry mouth, dizziness, fall, and constipation.
Conclusions:
For these patients with OFF episodes and dyskinesia, Gocovri significantly reduced daily OFF time (-1.2 hours) and time spent in these disruptive motor states (-3.0 hours). Patient-reported function was significantly improved.