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.
Evaluate the ability of Gocovri® (amantadine) extended release capsules to reduce disruptive motor episodes (OFF and troublesome dyskinesia) and improve patient function.
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.
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.
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.
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.