Open-label titration of apomorphine sublingual film in patients with Parkinson's disease and "OFF" episodes. (October 2020)

• Record Type: Journal Article
• Authors: Hui, Jennifer S.; Fox, Susan H.; Neeson, William; Bhargava, Parul; Pappert, Eric; Blum, David; Navia, Bradford
• Is Part Of: Parkinsonism & related disorders. Volume 79(2020)
• Page Start: 110
• Page End: 116
• Publication Date: 2020-10
• Subjects: Apomorphine sublingual film -- Parkinson's disease -- "OFF" episode -- Titration; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2020.08.028
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: The efficacy and safety of apomorphine sublingual film (APL-130277; APL) for the on-demand treatment of "OFF" episodes associated with Parkinson's disease (PD) was demonstrated in a double-blind trial. Herein we describe the ability of patients to receive effective and tolerable APL dose titration during the open-label titration phase. Methods: Adult patients with levodopa-responsive PD and "OFF" episodes were enrolled. In practically defined "OFF, " patients were observed for a FULL "ON" after their usual morning carbidopa/levodopa (CD/LD) dose and then after titration with APL following each increasing dose (10–35 mg). Antiemetic medication was administered for 3 days before initiation of titration and was continued throughout titration. Motor responses were evaluated predose and postdose using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score. Safety outcomes were evaluated. Results: Among 141 patients who enrolled in the study and received APL during open-label titration, 109 (77.3%) achieved a FULL "ON" (66.1% at 10–20 mg) and 10 did not. Patients who successfully completed APL dose titration tended to be younger, had a longer mean time since PD diagnosis, and had lower levodopa requirements than those who discontinued during titration for any reason. Change in MDS-UPDRS Part III scores from predose to 30 min postdose after titration with the effective dose of APL (n = 109) was similar across all dose groups. In a post hoc analysis, the magnitude of motor response with APL was ~2-fold higher than with CD/LD 15 min postdose, and the observed peak response occurred earlier with APL than with the trend seen for CD/LD (45 vs 90 min, respectively). Overall, the most common (≥10%) treatment-emergent adverse events (TEAEs) during APL dose titration were nausea (20.6%), yawning (12.1%), dizziness (11.3%), and somnolence (11.3%). Twelve patients discontinued due to TEAEs during APL dose titration, most commonly (≥2%) because of dizziness (2.8%), nausea (2.1%), and somnolence (2.1%). Conclusion: Among eligible patients with PD and "OFF" episodes who had their APL dose successfully titrated to an effective and tolerable level, most were able to do so within the first 3 titrated doses but some required further dose escalations. The use of APL can provide benefit for the treatment of "OFF" episodes. Highlights: An effective and tolerable dose was achieved in the first 3 doses for most patients. Change (pre-to postdose) in MDS-UPDRS Part III was consistent across APL doses. APL resulted in a similar magnitude of response but faster onset of action vs CD/LD. APL was generally well tolerated during titration.