Objective: Evaluate long-term safety (LTS), tolerability, and efficacy of apomorphine sublingual film (APL-130277; APL) for on-demand treatment of “OFF” episodes in de novo (DN) vs rollover (RO) 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 in DN/RO subgroups have not been previously described.

Method: A multicenter, ongoing, open-label, Phase 3 study (NCT02542696) enrolled patients with PD (DN/RO from prior studies) and “OFF” episodes while on stable PD medications. APL dose titration (DT) occurred 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. Titrated dose was self-administered for up to 5 “OFF” episodes/d in the LTS phase. Primary endpoint was incidence of TEAEs in DT+LTS phases. Secondary endpoints were change from predose in MDS-UPDRS Part III score and percentage with self-rated FULL “ON” within 30 min postdose at in-office visits at wks 24, 36, and 48.

Results: Interim safety (data cut May 2019) included 347 DN/78 RO patients; interim efficacy included 275/70 who received ≥1 dose of APL during the LTS phase (median exposure: 115/170 d). TEAEs in DN vs RO patients were similar (84%/85%); most common (≥10%): nausea (26%/31%), yawning (12%/14%), somnolence (11%/12%), dizziness (10%/15%), and fall (6%/10%). Most common oral TEAEs (≥5%) were mucosal erythema (8%/9%), lip swelling (5%/3%), mouth ulceration (5%/3%), and swollen tongue (3%/5%). TEAEs leading to D/C were more frequent in DN patients (32%/24%); most common were nausea (5%/10%), lip swelling (4%/0%), and dizziness (2%/3%). Deaths occurred in 3 DN/1 RO patient (unrelated to drug). Changes from predose in mean MDS-UPDRS Part III scores at wk 24 were –13.7/–12.2 at 15 min, –19.6/–21.6 at 30 min, and –18.0/–22.4 at 60 min; results were similar at wks 36 and 48. FULL “ON” by 30 min postdose was observed in 77%/65% at wk 24, 92%/75% at wk 36, and 91%/67% at wk 48.

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, with few notable differences between DN and RO patients.

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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-de-novo-vs-rollover-patients-with-parkinsons-d/