Evaluate bedtime-administered, delayed-release/extended-release amantadine (AMT DR/ER) capsules for motor complications in people with Parkinson’s disease (PD; PwP) who may be candidates for device-aided therapy (DAT).

The 5-2-1 criteria (≥5 levodopa doses, ≥2 hours OFF/day, and ≥1-hour dyskinesia/day) propose to identify PwP poorly controlled on oral therapies who may benefit from optimized treatment, including DAT. AMT DR/ER is the only medication FDA-approved for dyskinesia and OFF episodes in levodopa-treated PwP.

Week-12 treatment differences (AMT DR/ER − placebo) in UDysRS, MDS-UPDRS Parts II and IV, 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 (Week 100) open-label trial, where MDS-UPDRS Part IV scores were measured relative to double-blind baseline.

Of 198 enrolled participants, 53% used levodopa ≥5 times/day, 60% recorded ≥2 hours/day OFF time, 99% recorded ≥1 hour/day troublesome dyskinesia, and 32% (n=64) met all 3 criteria and composed the 5-2-1 cohort. Compared to overall participants, the 5-2-1 cohort was younger at PD diagnosis and start of levodopa therapy, had dyskinesia longer, had more daily OFF time, and used higher levodopa doses. At Week-12 endpoint, AMT DR/ER significantly improved UDysRS scores (−9.2; P=.006), reduced OFF time (−1.4 hours/day; P=.02) and troublesome dyskinesia (−1.6 hours/day; P=.04), and improved ”Good” ON time without troublesome dyskinesia (2.8 hours/day; P=.003) relative to placebo. Treatment benefit was sustained through open-label, follow-on trial Week 100, with MDS-UPDRS Part IV score improvements of −5.0 (former placebo-group) and −3.2 (continuing AMT DR/ER group); 45% of the 5-2-1 cohort completed both trials (through Week 100). AMT DR/ER adverse events included peripheral edema, falls, dizziness, hallucinations, and dry mouth.

Findings suggest AMT DR/ER should be considered as an option for PwP eligible for DAT.