Objective: Evaluate effect of apomorphine sublingual film (APL-130277; APL) as an on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD) on MDS-UPDRS Part III subdomains.

Background: In a pivotal study (NCT02469090), APL significantly improved the primary end point of change from predose to 30 min postdose in MDS-UPDRS Part III score at wk 12 vs placebo (–11.1 vs –3.5; LSM difference, –7.6; P=0.0002).

Method: Patients with PD and “OFF” episodes on stable PD medications were enrolled and treated with APL while in a practically defined “OFF” state. The optimized APL dose (10–35 mg) that resulted in a FULL “ON” by 45 min was determined during open-label titration. Patients were then randomized to that APL dose or matching placebo in a double-blind maintenance phase for 12 wks. This post hoc analysis evaluated the change from predose to 30 min postdose in MDS-UPDRS Part III motor subdomain scores at wk 12 in the modified intention-to-treat population. Strength of association between change in subdomain and total MDS-UPDRS Part III scores was evaluated by Pearson’s correlation coefficient.

Results: Analysis included 109 patients (APL, n=54 [median exposure, 84 d]; placebo, n=55 [median exposure, 85 d]). The predose mean Part III scores were 11.6 (APL) vs 12.3 (placebo) for midline function, 4.5 vs 4.0 for rest tremor, 7.0 vs 7.7 for rigidity, 5.3 vs 5.4 for right upper extremity (RUE) bradykinesia, 5.5 vs 5.8 for left upper extremity (LUE) bradykinesia, 2.5 vs 1.4 for postural and kinetic tremors, and 6.9 vs 7.4 for lower limb bradykinesia. Mean changes in Part III scores from predose to 30 min postdose at wk 12 were –2.7 (APL) vs –1.3 (placebo) for midline function (r=.65 vs .73), –1.3 vs –0.6 for rest tremor (r=.36 vs .47), –1.9 vs –0.7 for rigidity (r=.61 vs .88), –1.4 vs –0.3 for RUE bradykinesia (r=.81 vs .76), –0.7 vs –0.4 for LUE bradykinesia (r=.53 vs .71), –1.0 vs –0.1 for postural and kinetic tremors (r=.19 vs .34), and –1.1 vs –0.5 for lower limb bradykinesia (r=.70 vs .78).

Conclusion: Apomorphine sublingual film as an on-demand treatment of “OFF” episodes in patients with PD resulted in improved motor function across all MDS-UPDRS Part III subdomains vs placebo in a pivotal study, with the greatest postdose effect on midline function.

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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-effect-on-mds-updrs-part-iii-subdomains/