Objective: To evaluate the efficacy of APL-130277 (APL) in a double-blind, placebo-controlled trial.

Background: OFF episodes are a common, disabling complication of Parkinson’s disease (PD) despite available therapies. APL is a sublingual formulation of apomorphine being developed for the acute treatment of all types of OFF episodes.

Methods: A 12-week, adequate and well-controlled, double-blind Phase 3 trial was conducted, in patients with PD receiving levodopa who were experiencing motor fluctuations, to evaluate the efficacy of APL for the acute treatment of OFF episodes. The APL dose (10-35 mg) to produce a FULL ON response was determined in the titration phase. Patients were then randomized at the titrated dose to APL or placebo for 12 weeks, dosing up to 5x/day. MDS-UPDRS Part III motor score was determined pre-dose and at 15, 30, 45, 60 and 90 minutes post-dose at monthly assessment visits. The primary endpoint was the change in MDS-UPDRS Part III score at 30 mins post dose after 12-weeks of treatment. The key secondary endpoint was the percentage of patients with a patient-determined FULL ON within 30 mins at 12-weeks. The endpoints were tested using Mixed -Effect Model Repeated Measures in a hierarchical manner in the mITT population.

Results: One-hundred and nine patients who completed the titration phase were randomized (placebo-55, APL-54). 80 patients completed the study (placebo-46 and APL-34). The LS Mean (SE) change from pre-dose to 30 min post-dose for the MDS-UPDRS Part III score at 12 weeks was -11.1 (1.5) and -3.5 (1.3) for the APL and placebo groups, respectively (mean difference = -7.6; p=0.0002). Similar results were observed at day 1, weeks 4 and 8. Separation from placebo was observed as early as 15 mins and persisted up to 90 mins, the last assessment time point. There was also a significant difference favoring APL over placebo in the percentage of patients who rated themselves as FULL ON at 30 mins at 12-weeks (p=0.04). Additional supportive findings favoring APL included percent of patients ON within 30 mins who remained ON for at least 30 mins, the CGI, PGI and the Home Diary which showed that a larger percentage of APL-treated patients (LS mean 78.70%) turned ON within 30 mins post-dose compared to placebo (LS mean 31.10%).

Conclusions: The results of this Phase 3 study demonstrated a clinically meaningful benefit of APL treatment in patients with PD experiencing OFF episodes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-sublingual-apomorphine-film-apl-130277-for-the-treatment-of-off-episodes-in-patients-with-parkinsons-disease-results-from-the-phase-3-double-blind-placebo-controlled-trial/