Objective: Evaluate the long-term safety (LTS), tolerability, and efficacy of apomorphine sublingual film (APL-130277; APL) for on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD).

Background: In a 12-wk pivotal study, APL was efficacious and generally well tolerated for on-demand treatment of “OFF” episodes in patients with PD. LTS and efficacy have not been previously described.

Method: A multicenter, ongoing, open-label, Phase 3 study (NCT02542696) enrolled patients with PD (de novo or rollover from prior Phase 2/3 studies) and “OFF” episodes while on stable PD medications. APL dose titration (DT) occurred while in a practically defined “OFF” state in the morning to determine the dose (10–35 mg; 5-mg increments) that converted patients to FULL “ON” by 45 min. In the LTS phase, patients self-administered their titrated APL dose for up to 5 “OFF” episodes/d. Primary endpoint was incidence of TEAEs in DT+LTS phases. Secondary endpoints included change from predose in MDS-UPDRS Part III score and percentage of patients with a self-rated FULL “ON” within 30 min postdose at in-office visits at wks 24, 36, and 48.

Results: Interim safety analysis (data cut May 2019) included 425 patients; interim efficacy included 345 patients who received ≥1 APL dose during the LTS phase (median [range] exposure: 141 [1–723] d); 67% were titrated within the first 3 doses. TEAEs occurred in 85% of patients, most (66%) were mild and the most common (≥10%) included nausea (27%), yawning (12%), dizziness (11%), and somnolence (11%). The most common oral TEAEs (≥5%) were mucosal erythema (8%) and lip swelling (5%). Syncope occurred in 2%. TEAEs leading to discontinuation occurred in 31%; the most common were nausea (6%), lip swelling (3%), and dizziness (2%). Deaths were reported in 4 patients; none were considered drug related. At wk 24, the changes from predose in mean MDS-UPDRS Part III scores at 15, 30, and 60 min were –13.3, –20.1, and –19.2 points, respectively. Similar results were observed at wks 36 and 48. Patient-rated FULL “ON” was observed in 74%, 89%, and 84% of patients by 30 min postdose at wks 24, 36, and 48, respectively.

Conclusion: Interim results up to 48 wks support the LTS and efficacy of apomorphine sublingual film as an on-demand treatment of “OFF” episodes in patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-long-term-safety-tolerability-and-efficacy-study-of-apomorphine-sublingual-film-for-on-demand-treatment-of-off-episodes-in-patients-with-parkinsons-disease-interim-resu/