Category: Parkinson’s Disease: Clinical Trials
Objective: Evaluate long-term safety (LTS), tolerability, and efficacy of apomorphine sublingual film (APL) for on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD) from Europe (EU) and North America (NA).
Background: In a 12-wk pivotal study, APL was efficacious and generally well tolerated for treatment of “OFF” episodes in patients with PD. LTS and efficacy in EU/NA subgroups have not been previously described.
Method: An ongoing, open-label, Phase 3 study (NCT02542696) enrolled patients with PD (new or rollover from prior studies) and “OFF” episodes while on stable PD medications. APL dose titration occurred in patients who were “OFF” to determine the effective and tolerable dose (10–35 mg; 5 mg increments) that converted them to FULL “ON” within 45 min. In the LTS phase, patients self-administered their titrated APL dose for up to 5 “OFF” episodes/d. Endpoints included TEAEs in the LTS phase (primary), change from predose in MDS-UPDRS Part III score, and percentage of patients with self-rated FULL “ON” within 30 min postdose at wks 24, 36, and 48.
Results: This analysis (data cut 30Sep2020) evaluated 63 EU/334 NA patients who received ≥1 APL dose (40%/40%, 16%/26%, and 3%/12% for >6, >12, and >24 mos) during the LTS phase. Baseline demographics and PD history were generally similar, except for greater use of dopamine agonists (91%/57%) and MAO-B inhibitors (61%/44%) in EU. The incidence of overall TEAEs was similar (81%/84%). Incidences of dyskinesia (6%/6%), vomiting (3%/4%), and hypotension (2%/1%) were similar, while nausea (6%/24%), dizziness (3%/7%), orthostatic hypotension (2%/4%), and somnolence (2%/8%) were higher in NA, and oral TEAEs (44%/38%) were higher in EU. Change in Part III score at 30 min postdose was greater in EU vs NA patients at wks 24 (–28.5/–20.1), 36 (–28.2/–19.6), and 48 (–30.0/–20.5), and in general across other time points up to 90 min, with clinically meaningful changes observed as early as 15 min postdose. Overall, most patients (>75%) achieved FULL “ON” within 30 min postdose through 48 wks.
Conclusion: Interim results up to 48 wks with apomorphine sublingual film treatment showed that despite differences in concomitant PD therapies, EU patients experienced more robust long-term efficacy and a similar safety profile as NA patients, with lower rates of nausea, dizziness, orthostatic hypotension, and somnolence.
To cite this abstract in AMA style:R. Pahwa, S. Fox, J. Hui, C. Singer, J. Schwarz, M F. de Pandis, J. Raw, I. Zhang, E. Pappert, B. Navia. Long-Term Safety and Efficacy of Apomorphine Sublingual Film for “OFF” Episodes in Parkinson’s Disease: Europe vs North America [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/long-term-safety-and-efficacy-of-apomorphine-sublingual-film-for-off-episodes-in-parkinsons-disease-europe-vs-north-america/. Accessed December 7, 2023.
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