Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
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.
To cite this abstract in AMA style:C. Olanow, F. Stocchi, K. Wilks, E. Peckham, M. de Pandis, K. Sciarappa, R. Kleiman, D. Blum, B. Navia. Efficacy, Safety, and Tolerability of Supratherapeutic Doses of Apomorphine Sublingual Film for the Treatment of “OFF” Episodes in Patients With Parkinson’s Disease [abstract]. Mov Disord. 2019; 34 (suppl 2). 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/. Accessed December 7, 2023.
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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/