Objective: Evaluate effect of apomorphine sublingual film (APL-130277; APL) on impulse control disorders (ICD) in patients with Parkinson’s disease (PD) and “OFF” episodes.

Background: In a pivotal controlled (PC) study, APL significantly improved MDS-UPDRS Part III score at wk 12 vs placebo (LSM difference, –7.6; P=0.0002). However, dopaminergic agents have been associated with ICD.

Method: Patients with PD and “OFF” episodes on stable PD medications (eg, oral/transdermal dopamine agonists) were enrolled in the PC (NCT02469090) and/or ongoing long-term safety (LTS; NCT02542696) study. Patients in a practically defined “OFF” state received APL (optimized dose [10–35 mg] that resulted in a FULL “ON” within 45 min determined during open-label titration) or matching placebo for 12 wks (PC study), or APL (optimized as before) for ≤48 wks (LTS study). ICD were assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease – Rating Scale (QUIP-RS). Results were summarized descriptively and assessed at wk 12 (PC study, maintenance phase) and at wks 24, 36, and 48 (LTS study, data cut May 2019).

Results: Analysis populations included 109 patients in the PC study (APL, n=54 [median (range) exposure: 84 (1–126) d; 2.2 mean doses/d]; placebo, n=55 [exposure: 85 (1–106) d; 2.5 doses/d]) and 345 in the LTS study (exposure: 141 [1–723] d; 1.8 doses/d). In the PC study, mean (SD) baseline total ICD scores were 5.4 (6.57) for APL and 6.3 (7.01) for placebo and wk 12 changes from baseline were –1.3 (5.57) and –1.5 (6.20); baseline total QUIP-RS scores were 9.2 (10.18) and 11.8 (14.10) and wk 12 changes from baseline were –0.8 (10.92) and –2.8 (13.76). For APL, incidence of individual ICD decreased or remained similar from screening to wk 12 for all except gambling. In the LTS study, mean (SD) baseline total ICD score was 5.7 (6.75) and changes from baseline were –0.3 (6.71), –1.6 (7.12), and 0.6 (6.01) at wks 24, 36, and 48; baseline total QUIP-RS score was 10.6 (12.25) and changes from baseline were –1.7 (12.58), –4.8 (14.56), and 0.3 (12.65) at wks 24, 36, and 48. Incidence of individual ICD either decreased or remained similar from screening to wk 48 for all.

Conclusion: The addition of apomorphine sublingual film as an on-demand treatment for “OFF” episodes in patients with PD had minimal impact on ICD over a period of up to 48 wks in 2 Phase 3 studies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apomorphine-sublingual-film-for-on-demand-treatment-of-off-episodes-in-patients-with-parkinsons-disease-impact-on-impulse-control-disorders/