Abstract Details

AMT DR/ER is approved to treat dyskinesia in PD. Based on significant reductions in OFF time in dyskinesia clinical trials, the FDA granted AMT DR/ER an additional indication as a levodopa-adjunct to treat OFF episodes. OFF episodes can emerge within the first years of levodopa use, so is important to evaluate AMT DR/ER efficacy as an early add-on to levodopa.

Utilize clinical trial data to evaluate amantadine delayed release/extended release (AMT DR/ER) as an early add-on for motor complications (OFF and dyskinesia) in Parkinson’s disease (PD).

Using pooled phase 3 pivotal trials, we estimated the efficacy of early AMT DR/ER use by evaluating PD diary outcomes for 2 participant subgroups: 1) those using levodopa monotherapy at baseline (levodopa-only), and 2) those diagnosed with PD within 5 years (PD ≤5 years). Efficacy for AMT DR/ER vs placebo was evaluated for each subgroup relative to overall pooled trial results.

Of 196 patients, 44 (22%; n=28 AMT DR/ER; n=16 placebo) composed the levodopa-only, and 27 (13.8%; n=14; n=13) the PD ≤5 years subgroup; 9 patients were included in both. The levodopa-only subgroup had similar and statistically significant placebo-adjusted improvements as overall trial participants in OFF time (−1.1 hours vs −1.0 hour), ON time with (−1.7 hours vs −1.5 hours) and without troublesome dyskinesia (2.5 hours vs 2.4 hours); PD ≤5 years had larger improvements (−1.5, −3.3, and +5.1 hours, respectively) that were also statistically significant. The most common adverse events with AMT DR/ER, overall and for each subgroup, included hallucinations, dizziness, dry mouth, peripheral edema, constipation and (for ≤5 years subgroup) livedo reticularis.

Reductions in OFF time and troublesome dyskinesia, and accompanying improvement in “Good” ON time without troublesome dyskinesia in these patient subgroups suggests AMT DR/ER efficacy as a first add-on to levodopa in patients with early motor complications.