Amantadine Reduces Off Time, Disruptive Motor States in Parkinson Disease

Robert A. Hauser, MD, MBA

Data from a post-hoc analysis of 2 pooled phase 3 trials (NCT02136914; NCT02274766) submitted for the 2020 American Academy of Neurology (AAN) Annual Meeting revealed that treatment with amantadine (Gocovri; Adamas Pharmaceuticals) extended-release capsules significantly reduced daily “off” time and time spent in Parkinson disease (PD) disruptive motor states in those with PD.^1,2

Among the 198 patients enrolled in the trial, 101 (51%) of those composing the “off” subgroup had dyskinesia and ≥2.5 hours of daily “off” time. At baseline, the 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 a reduction of 1.2 hours (P <.001) and troublesome dyskinesia was reduced by 2.0 hours (P <.001).

Researchers noted that the improvement in good “on” time was due to a reduction in the number of hours spent in “off” as well as the hours spent “on” with troublesome dyskinesia. Patient-rated motor symptom impact on activities of daily living were significantly improved compared to placebo as shown by a —3.2 change on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS; P <.001).

Treatment with amantadine resulted in 1.7 fewer disruptive episodes (P = .02) and 3.0 fewer hours per day spent in disruptive PD motor states (P <.001). Patient-rated dyskinesia disability measured by the Unified Dyskinesia Rating Scale (UDysRS) showed significant improvement with amantadine compared with placebo (change, —4.8; P <.001).

“This presentation aims to provide additional insights on the effect of Gocovri in reducing ‘off’ time for patients with Parkinson’s disease,” lead author Robert A. Hauser, MD, MBA, professor of Neurology, director, USF Parkinson’s Disease and Movement Disorders Center Parkinson Foundation Center of Excellence, said in a statement. “For clinicians seeking to improve management of ‘off’ and dyskinesia for patients without adjusting levodopa doses, these results suggest GOCOVRI could be an important treatment option.”

Adverse events (AEs) were consistent with the known safety profile of amantadine. In total, 44 (81.5%) patients who received the treatment reported at least 1 AE and 33 (61.1%) reported study drug-related AEs as well. Serious AEs were observed in 5 (9.3%) patients in the treatment population, with 10 (18.5%) discontinuing the trial due to drug-related AEs.

Patients included in the analysis not only had ≥2.5 hours of “off” time at baseline, but also had at least 2, 30-minute periods of troublesome dyskinesia per day. Amantadine-placebo treatment differences were analyzed at week 12 and included measures such as a PD diary, UDysRS, MSD-UPDRS Parts II and IV.

Adamas Pharmaceuticals released data on EASE LID 2, its 2-year, open-label, trial of amantadine in February which showed long-term safety and tolerability, as well as a durable reduction in the motor complications of PD.

The results showed that at baseline, MDS-UPDRS Part IV scores were a mean of 6.5 points for those continuing treatment with amantadine compared to 9.4 for the placebo group and 10.5 for the deep brain stimulation group. By Week 8, every group had similar scores—amantadine: 6.3; placebo: 6.2; deep brain stimulation: 6.4&mdash;and remained level for the amantadine group at Week 100, at 6.9 points, compared to 7.3 and 7.0 for the placebo and deep brain stimulation groups, respectively.³

REFERENCES

1. Adamas presents new post-hoc phase 3 data analysis for Gocovri in Parkinson’s disease at the 2020 American Academy of Neurology (AAN) science highlights platform [news release] Emeryville, CA. Adamas Pharmaceuticals. Published July 15, 2020. Accessed July 20, 2020. globenewswire.com/news-release/2020/07/15/2062508/0/en/Adamas-presents-new-post-hoc-Phase-3-data-analysis-for-GOCOVRI-in-Parkinson-s-disease-at-the-2020-American-Academy-of-Neurology-AAN-Science-Highlights-Platform.html

2. Hauser R. Chernick D, Formella A. Gocovri reduces disruptive motor episodes and improves function in Parkinson’s disease patients with OFF episodes and dyskinesia: analysis of phase 3 trial data. Neurology. 2020;94(15 Suppl): 1882.

3. Adamas Announces Publication of the Two-Year Phase 3 Open-Label EASE LID 2 Trial of GOCOVRI® for Dyskinesia in Patients with Parkinson’s Disease. [press release]. Emeryville, CA. Adamas Pharmaceuticals. Published February 11, 2020. Accessed July 20, 2020. globenewswire.com/news-release/2020/02/11/1983417/0/en/Adamas-Announces-Publication-of-the-Two-Year-Phase-3-Open-Label-EASE-LID-2-Trial-of-GOCOVRI-for-Dyskinesia-in-Patients-with-Parkinson-s-Disease.html.