Evaluate efficacy and safety of apomorphine sublingual film (APL) as an acute, intermittent therapy for “OFF” episodes in patients with Parkinson’s disease (PD) in a phase 3, double-blind, placebo-controlled trial.

Most patients receiving chronic levodopa treatment develop motor fluctuations with “OFF” episodes. A phase 2 study suggested that APL is efficacious for treatment of individual “OFF” episodes.

Adult patients with PD and ≥1 “OFF” episode per day while on stable doses of levodopa/adjunctive PD medications received increasing doses of APL (10–35 mg) in an open-label titration phase until a FULL “ON” response was achieved. Patients were randomized to placebo or APL at the dose determined during titration for 12 weeks. The primary endpoint was change from predose to 30 minutes postdose in MDS-UPDRS Part III Motor Examination score at week 12. The key secondary endpoint was the percentage of patients with a self-rated FULL “ON” response within 30 minutes at week 12.

109 patients who completed the open-label titration phase were randomized in the double-blind treatment phase (APL=54, placebo=55). Least squares mean ± standard error change from predose to 30 minutes postdose in MDS-UPDRS Part III at week 12 was –11.1 ± 1.46 with APL and –3.5 ± 1.29 with placebo (difference, –7.6 points; P=0.0002). Separation from placebo was seen as early as 15 minutes and persisted up to the 90-minute timepoint. The self-rated FULL “ON” response rate within 30 minutes postdose at week 12 was significantly higher for APL versus placebo (35% vs 16%; P=0.0426). The most common APL-associated, treatment-emergent adverse events (TEAEs) were nausea (28%), somnolence (13%), and dizziness (9%); the most common oral TEAE was oral mucosal erythema (7%); most TEAEs were mild and reversible upon treatment discontinuation.

APL was an efficacious and well-tolerated treatment for the acute, intermittent management of “OFF” episodes associated with PD.