Abstract | BACKGROUND: The 5-2-1 criteria (≥5 levodopa doses/day, ≥2 h OFF/day, and ≥ 1-hour dyskinesia/day) propose to identify people with Parkinson's disease (PD) who are poorly controlled on oral therapies and who may therefore benefit from device-aided therapies. Amantadine-DR/ER is the only medication FDA-approved for both dyskinesia and OFF episodes in levodopa-treated patients. In this post-hoc analysis of phase 3 clinical trials, we evaluated the efficacy and safety of amantadine-DR/ER in patients meeting 5-2-1 criteria. METHODS: Week-12 treatment differences ( Amantadine-DR/ER - placebo) in the Unified Dyskinesia Rating Scale (UDysRS) and PD motor states (patient diaries) were evaluated in pooled, phase-3, double-blind trial participants meeting 5-2-1 criteria at baseline. This 5-2-1 cohort was followed into a 2-year open-label trial, where Movement Disorder Society - Unified Parkinson's Disease Rate Scale (MDS-UPDRS) Part IV scores were assessed relative to double-blind baseline. RESULTS: Of 198 enrolled participants in the phase 3 trials, 65 (33%; n = 29 placebo; n = 36 amantadine-DR/ER) comprised the 5-2-1 cohort. At Week-12 endpoint, amantadine-DR/ER significantly improved UDysRS scores (treatment difference of 9.57 ± 3.15 points, p = 0.004) and ON time without troublesome dyskinesia ('good ON', treatment difference of 2.9 ± 0.90 h/day, p = 0.002). Improvements in good ON time resulted from significant reductions in both troublesome dyskinesia and OFF time. Treatment benefit on MDS-UPDRS-Part IV was sustained through open-label, follow-up. The most common adverse events in patients who met 5-2-1 criteria and were treated with amantadine-DR/ER included falls and peripheral edema. CONCLUSIONS: Findings suggest Amantadine-DR/ER should be considered as an option for people with PD who meet 5-2-1 criteria.
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Authors | Robert A Hauser, Santosh Goud, Andrea E Formella |
Journal | Clinical parkinsonism & related disorders
(Clin Park Relat Disord)
Vol. 6
Pg. 100123
( 2022)
ISSN: 2590-1125 [Electronic] England |
PMID | 35059622
(Publication Type: Journal Article, Review)
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Copyright | © 2021 The Authors. |