Objective: To evaluate the effect of treatment with amantadine delayed release/extended release (AMT DR/ER) vs. placebo on the proportion of the waking day spent in “BAD” time (defined as ON time with troublesome dyskinesia + OFF time [1]) in patients with Parkinson Disease (PwPD) enrolled in the pivotal trials of AMT DR/ER for dyskinesia [2,3].

Background: Current treatment algorithms for the treatment of PwPD often present a difficult trade-off between balancing OFF time and managing dyskinesia. AMT DR/ER is the only FDA-approved medication to treat both dyskinesia and OFF episodes in PwPD who are also taking levodopa.

Method: We evaluated the combined reductions in dyskinesia and OFF time in AMT DR/ER clinical trials using several methods for PwPD who completed the week 12 visit. (1) Evaluated were the percent of the waking day spent in these states and changes in the ratio of OFF and troublesome dyskinesia and, (2) using ≥25%, ≥50% and ≥75% response thresholds.

Results: At baseline, “BAD” time accounted for a mean of 49% (placebo) and 48% (AMT DR/ER) of the waking day, and the mean ratio of troublesome dyskinesia/OFF time was 68%/32% for placebo and 61%/39% for AMT DR/ER. Treatment with AMT DR/ER statistically significantly (P<.001) decreased the percent of day spent in “BAD” motor states; after 12 weeks of treatment with AMT DR/ER “BAD” time accounted for 24% of the waking day, and the relative ratio of dyskinesia/OFF reversed to 31%/69%. By contrast, for patients treated with placebo, “BAD” time accounted for 39% of the waking day, and the dyskinesia/OFF ratio was 49%/51%. Likewise, significantly more subjects met responder thresholds: for AMT DR/ER vs. placebo; 77% vs. 47% (P<.0001) had a at least a 25% reduction in “BAD” time, 58% vs. 29% (P=.02) had at least a 50% reduction and 32% vs. 16% (P<.001) at least a ≥75% reduction.

Conclusion: PwPD enrolled in dyskinesia studies also spend a large portion of their waking day in the OFF state. Treatment with AMT DR/ER reduced the daily time PwPD spent in “BAD” motor states by one-half.

References: [1] Hauser et al. Mov Disord. 2004;19(12):1409-13.
[2] Pahwa et al. JAMA Neurol. 2017;74(8):941-9.
[3] Oertel et al. Mov Disord. 2017;32(12):1701-9.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/amantadine-delayed-release-extended-release-capsules-reduce-the-proportion-of-the-day-spent-in-bad-time-on-with-troublesome-dyskinesia-or-off-analysis-of-phase-3-trial-data/