Objective: Evaluate safety/onset of efficacy during titration of continuous subcutaneous apomorphine infusion (CSAI) for motor fluctuations in U.S. outpatients with Parkinson’s disease (PD).

Background: Global use of CSAI has shown safety/tolerability during titration, but clinical experience in the US is limited. CSAI provides antiparkinsonian response similar to levodopa; subcutaneous delivery more reliably allows for a continuous dopaminergic effect.

Method: We evaluated outpatient initiation and titration of CSAI in the U.S. InfusON trial enrolling levodopa-treated PD patients with persistent motor fluctuations despite optimized oral medication regimens (NCT02339064). CSAI was initiated with a 1-2 mg bolus (≥3h after the last levodopa dose) followed by a 1 mg (0.2mL)/h infusion. Infusion rate could be adjusted in 0.5 to 1 mg/h increments over the next 3-5 visits, according to clinical response and tolerability, up to a maximum 8 mg/h and up to 3 daily bolus doses, with total dose not to exceed 150 mg/day.

Results: Of 99 patients treated, 85 completed titration. Median time to complete CSAI titration ­­was 30 days. Other PD medications were reduced in 48 patients (median CSAI rate at first reduction: 2 mg/h). At baseline, mean daily OFF time was 6.6 h/day (n=94). Improvement began upon CSAI initiation, with OFF time reductions of -0.9 h/day (n=82) by the first titration visit and -1.7 h/day (n=92) by the second visit. OFF reduction was -2.8 h/day by the end of titration – a 39% reduction (n=80). An improvement in ON time without troublesome dyskinesia of 0.7 h/day was also observed by the first visit and reached 3.0 h/day by end of titration – a 43% increase. Treatment-related adverse events included infusion site nodules (63.6%), dyskinesia (29.3%), nausea (24.2%), infusion site erythema (22.2%), dizziness (18.2%) and somnolence (17.2%); 17 patients (17.2%) discontinued during titration, most commonly for infusion site nodules [4%] and nausea [3%].

Conclusion: Improvement in OFF time and Good-ON time were observed at the first titration visit. Improvement continued throughout the 1-year Maintenance phase consistent with durable treatment effect.  Titration was well-tolerated with 86% of initiated patients successfully entering the Maintenance phase.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-onset-of-efficacy-during-titration-in-us-phase-3-open-label-infuson-trial-of-apomorphine-subcutaneous-infusion-for-parkinsons-disease-motor-fluctuations/