Objective: To evaluate efficacy, safety, and tolerability of supratherapeutic doses of apomorphine sublingual film (APL-130277; APL) in patients with Parkinson’s disease (PD) and “OFF” episodes.

Background: Patients with PD develop “OFF” episodes, a common complication that may negatively impact quality of life. APL was found to be effective and generally well tolerated in a 12-week, double-blind, placebo-controlled, randomized Phase 3 trial.

Method: Patients with PD on stable medications without antiemetics who demonstrated drug withdrawal–induced “OFF” episodes were eligible. Patients received increasing doses of APL (10–60 mg) until a FULL “ON” response was achieved, and then received 2 additional supratherapeutic doses, if tolerated (maximum 60 mg). Differences in efficacy between the lowest dose resulting in a FULL “ON” response (low) and the highest supratherapeutic dose received (high), if different, were explored by comparing changes in Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III scores from predose to 30, 60, and 90 minutes postdose using a Repeated Measurements model. Time to and duration of FULL “ON” were evaluated using Kaplan-Meier analysis.

Results: Forty-eight patients received ≥1 dose of APL (safety population); 35 were evaluable for exploratory efficacy analyses. The dose to FULL “ON” was ≤20 mg for 79% of patients. Superior mean reduction in MDS-UPDRS Part III scores was observed for high- vs low-dose APL (least squares mean ± standard error difference was –5.5±2.47; P=0.0325,–4.9±1.63; P=0.0052, and –3.7±1.50; P=0.0190 at 30, 60, and 90 minutes postdose, respectively). Median time to FULL “ON” (30 minutes), earliest observed time to FULL “ON” (10 minutes), and probability of patients with a FULL “ON” duration of ≥50 minutes (~90%) were similar between doses. The most common treatment-emergent adverse events (TEAEs) were nausea (56%), somnolence (25%), vomiting (19%), and dizziness (17%); these were generally transient and mild to moderate in severity. No serious TEAEs or deaths were reported.

Conclusion: Administration of APL at doses above those necessary to produce an apparent FULL “ON”, without antiemetics, may provide additional benefits in the treatment of “OFF” episodes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-safety-and-tolerability-of-supratherapeutic-doses-of-apomorphine-sublingual-film-for-the-treatment-of-off-episodes-in-patients-with-parkinsons-disease/