Safety and Efficacy of Continuous Apomorphine Infusion in Patients with Parkinson's disease: Results from a Phase 3, Open-label Study
Isaacson S, Espay A, Pahwa R, Clinch T, LeWitt PA. Safety and Efficacy of Continuous Apomorphine Infusion in Patients with Parkinson's disease: Results from a Phase 3, Open-label Study. Neurology 2020; 94(15):4.
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.