Objective: To evaluate the safety of APL-130277 (APL) in the double-blind, placebo-controlled trial Titration Phase (TP) and Maintenance Phase (MP).

Background: OFF episodes are a common, disabling complication of Parkinson’s Disease (PD). APL is a sublingual formulation of apomorphine being developed for the acute treatment of all types of intermittent OFF episodes. A phase 3 trial was recently completed to evaluate the efficacy and safety of APL in PD patients with 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 TP. Patients were then randomized at the titrated dose to APL or placebo for 12 weeks, dosing up to 5x/day. Safety assessments included adverse events (AE), vital signs, ECG and laboratory and were collected during the TP and the 12-week MP.

Results: 141 patients were enrolled in the study. The most common AEs in the TP were nausea (20.6%), yawning (12.1%), somnolence (11.3%), and dizziness (11.3%). 109 subjects (placebo-55 and APL-54) were randomized in the MP. Fifteen (27.8%) and 5 (9.1%) subjects discontinued treatment due an AE in the APL and placebo groups, respectively. The most common AEs that led to discontinuation in the APL group during the MP were lip swelling (n=2), oral mucosal erythema (n=2) and oropharyngeal swelling (n=2). The most frequently reported AEs, by preferred term, during the MP for APL and placebo, respectively, were nausea: 27.8% and 3.6%; somnolence: 13% and 1.8%; and, dizziness: 9.3% and 0%. Most TEAEs, including nausea, were mild to moderate in severity. There were only 6 SAEs and 1 death. Oral AEs occurred in 31.5% of APL- and 7.3% of placebo-treated patients, respectively, and were the most common reason for study discontinuation. These events were generally mild to moderate and reversible, with study drug discontinuation. Orthostatic hypotension, hallucinations and dyskinesias were rare.

Conclusions: In this study of PD patients with OFF episodes, APL was generally well-tolerated over the 12-week study period. Oral AEs were the most commonly reported AE but were not severe. With the exception of oral events, the AE profile is largely consistent with the effects of other dopaminergic agents.

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