Effects of Gocovri (Amantadine) Extended-Release Capsules on Motor Aspects of Experiences of Daily Living in People with Parkinson's Disease and Dyskinesia

Abstract

Introduction: Gocovri, a bedtime-administered delayed-release/extended-release capsule formulation of amantadine, is the only drug approved by the US Food and Drug Administration as levodopa-adjunctive therapy for the treatment of OFF episodes and/or dyskinesia in Parkinson's disease (PD). Part II of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses patient-perceived disability on experiences of daily living affected by PD motor symptoms. We analyzed Gocovri-related changes in MDS-UPDRS Part II ratings in two placebo-controlled clinical trials.

Methods: Baseline to week 12 changes in MDS-UPDRS Part II total and item scores were compared for Gocovri and placebo using pooled data from phase 3 trials (EASE LID and EASE LID 3).

Results: Baseline mean MDS-UPDRS Part II total score was 15.1 for Gocovri (n = 100) and 15.3 for placebo (n = 96) groups. At week 12, the least squares mean change from baseline was -3.4 for the Gocovri group and -1.4 for placebo (treatment difference, -2.0; 95% CI -3.3 to -0.7; P = 0.004). For Gocovri, change from baseline exceeded a published minimal clinically important difference threshold of 3.05. Gocovri-related treatment differences over placebo were driven primarily by improvement in the scale items of freezing (-0.4; P < 0.0001), tremor (-0.4; P = 0.002), getting out of bed/car/deep chair (-0.3; P = 0.002), and eating tasks (-0.2; P = 0.016).

Conclusion: In addition to improvement in dyskinesia, Gocovri-treated participants experienced improvement in motor aspects of experiences of daily living. Analyses suggest that Gocovri may specifically improve freezing, tremor, getting out of bed/car/deep chair, and eating tasks.

Trial registration: ClinicalTrials.gov identifiers: NCT02136914, NCT02274766.

Keywords: Amantadine extended release; Experiences of daily living; Gocovri; MDS-UPDRS; Motor complications; Parkinson’s disease; Treatment.

© 2021. The Author(s).

Figures

Fig. 1

Distribution of MDS-UPDRS Part II M-EDL item scores for all participants at baseline. MDS-UPDRS Movement Disorder Society Unified Parkinson’s Disease Rating Scale, M-EDL motor aspects of experiences of daily living

Fig. 2

Time course of LS mean change from baseline in MDS-UPDRS Part II total score among all participants (pooled mITT population). The LS mean (SE) [Gocovri-placebo] treatment differences were: week 2: −1.8 (0.68) P = 0.009; week 8: −1.1 (0.68) ns; week 12: −2.0 (0.68); P = 0.004. P values are based on the comparison between Gocovri vs. placebo from the MMRM model with change from baseline as the dependent variable and the baseline value as a covariate. The model includes categorical effects for treatment group, study, and visit (weeks 2, 8, and 12), and the interaction between treatment group and visit. LS least squares, MDS-UPDRS Movement Disorder Society Unified Parkinson’s Disease Rating Scale, mITT modified intent to treat, MMRM mixed-effects model repeated measure, SE standard error

Fig. 3.

12-week changes in MDS-UPDRS Part II item scores: LS mean (95% CI) [Gocovri-placebo] treatment differences (pooled mITT population). P values are based on the comparison between Gocovri vs. placebo from the MMRM model with change from baseline as the dependent variable and the baseline value as a covariate. The model includes categorical effects for treatment group, study, and visit (weeks 2, 8, and 12), and the interaction between treatment group and visit. LS least squares, MDS-UPDRS Movement Disorder Society Unified Parkinson’s Disease Rating Scale, M-EDL motor aspects of experiences of daily living, mITT modified intent to treat, MMRM mixed-effects model repeated measure