Abstract
Objective: To investigate the safety and efficacy of apomorphine subcutaneous infusion in Parkinson’s disease (PD) patients inadequately controlled with levodopa and additional PD therapies.
Background: Although apomorphine infusion has been used internationally for >25 years, safety and efficacy data are absent in the US.
Design/Methods: This was an open-label, long-term outpatient study of apomorphine subcutaneous infusion at 18 US PD clinics (NCT02339064). PD patients with inadequate motor control despite optimized treatment with levodopa and additional PD therapy (including levodopa intestinal infusion and deep brain stimulation) were eligible for the study (≥3 hours of daily OFF time). Patients were titrated to individualized apomorphine dose to reach best waking day efficacy without intolerable adverse effects (AEs). Once the optimal infusion dose was identified, patients entered a 52 week open-label maintenance period. Safety and tolerability were assessed through AE reporting. The primary efficacy endpoint was change from baseline to maintenance Week-12 in daily OFF time.
Results: Ninety-nine patients (69.7% male, mean±SD age: 61.6±9.41 years, levodopa daily dose: 1041±487mg, time since diagnosis 13.6±8.5years, time with motor fluctuations: 10.3±9.3 years) were enrolled. Sixty-nine patients completed 12 weeks of maintenance treatment; 27 patients discontinued due to AEs before Week 12 (mostly during dose titration;n=17). The mean±SD daily apomorphine dose in the maintenance period through Week 12 was 50.5±23.4mg (3.6 mg per hour). After 12 weeks of treatment, the mean±SD daily OFF time diminished from 6.6±2.4 at baseline to 3.5±2.7 hours (mean±SD reduction of 3.0±3.2 hours, median: 3.2 hours), accompanied by a mean±SD increase of 3.1±3.4 hours in ON time without troublesome dyskinesia. Responder analysis showed that an OFF time reduction ≥2 hours was experienced by 62.1% of patients.
Conclusions: Maintenance treatment with apomorphine infusion was generally well-tolerated and associated with reduction in OFF time by about 2.5 hours compared to baseline.
Disclosure: Dr. Isaacson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acadia, Acorda, Adamas, Addex, Allergan, Amarantus, Axovant, Benevolent, Biogen, Britannia, Cerecor, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Intec, Ipsen, Jazz, Kyowa, Lundbeck, Michael J. Fox Foundation, Neurocrine, and NeuroDerm. Dr. Isaacson has received research support from AbbVie, Acadia, Acorda, Adamas, Addex, Allergan, Amarantus, Axovant, Benevolent, Biogen, Britannia, Cerecor, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Intec, Ipsen, Jazz, Kyowa, Lundbeck, Michael J. Fox Foundation, Neurocrine, and NeuroDerm.Dr. Espay has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Sunovion, Lundbeck, Osmotica Pharmaceutical, and USWorldMeds. Dr. Espay has received research support from NIH, Great Lakes Neurotechnologies, and the Michael J Fox Foundation. Dr. Pahwa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consulting fees from Abbott, Abbvie, ACADIA, Acorda, Adamas, Cala Health, Global Kinetics, Lundbeck, Neurocrine, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, US World Meds, Biogen, Boston Scientific, Cavion, Intec, Jazz, Kyowa, Lilly. Dr. Pahwa has received research support from has received research grants from Abbvie, Adamas, Avid, Biotie, Boston Scientific, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Dr. Clinch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with US WorldMeds. Dr. LeWitt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. LeWitt has served as a paid consultant for NeuroDerm Ltd. Dr. LeWitt has served as consultant or advisor (non-paid) for Acorda Therapeutics Adamas Pharmaceutical Biogen Inc.%2C%20Britannia%2C%20Bukwang%20Pharmaceutical%20Co.%2C%20Cavion%20Pharma%2C%20. Dr. LeWitt has received personal compensation in an editorial capacity for Paid for services as Editor-in-Chief of Clinical Neuropharmaco!ogy and not compensated for participation on editorial boards of Journal of Neural Neurodegeneration, and Journal of Parkinson’s Disease.. Dr. LeWitt has received research support from The Parkinson’s Disease and Movement Disorders Program that Dr. LeWitt directs has received clinical research grant support (for conducting clinical trials and other research) from AbbVie, Acorda, Adamas, Biotie, The Michael J. Fox Foundation for Parkinso.
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