Objective: To evaluate the efficacy and safety/tolerability of 24-hour/day continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa (a soluble formulation of levodopa/carbidopa prodrugs) vs oral levodopa/carbidopa in patients with advanced Parkinson’s disease (aPD).

Background: Foslevodopa/foscarbidopa delivers stable, individualized plasma levodopa concentrations.

Method: Patients with motor fluctuations inadequately controlled by their current medications were randomized 1:1 to receive optimized doses of either CSCI of foslevodopa/foscarbidopa plus oral placebo or CSCI of placebo solution plus oral immediate-release levodopa/carbidopa for 12 weeks (NCT04380142). Fixed sequence statistical testing was used for multiplicity control of efficacy endpoints.

Results: Baseline characteristics of the 141 patients were balanced between groups. Treatment with CSCI of foslevodopa/foscarbidopa produced significantly greater improvement at week 12 vs oral levodopa/carbidopa in “On” time without troublesome dyskinesia (model-based mean [SE] 2.7 [0.5] vs 1.0 [0.5] hours; P≤.01) and “Off” time (–2.8 [0.5] vs –1.0 [0.5] hours; P≤.01), mainly through improvements in “On” time without dyskinesia. Improvements in sleep (PDSS-2; −7.9 [1.2] vs −2.5 [1.1]; nominal P≤.001), QoL (PDQ-39; −6.4 [1.8] vs −2.3 [1.8]; nominal P≤.05), and a greater proportion of patients reporting being “On” upon awakening (83.0% vs. 36.7%) favoring foslevodopa/foscarbidopa were observed, but didn’t reach statistical significance after controlling for multiple testing. A majority of adverse events (AEs)−including infusion site AEs−were nonserious, and mild/moderate in severity. Infusion site AEs were the most common AEs reported in the foslevodopa/foscarbidopa group.

Conclusion: In aPD, treatment with CSCI of foslevodopa/foscarbidopa led to statistically significant, clinically meaningful improvement in motor fluctuations vs oral levodopa/carbidopa. Though changes in sleep, QoL, and morning akinesia were not significant after control for multiple analyses, observed numerical improvements suggest additional potential benefits of 24-hour CSCI and warrant further study. Foslevodopa/foscarbidopa was generally safe and well tolerated, with a systemic safety profile typical of levodopa/carbidopa. Infusion site AEs were similar to those observed with other subcutaneously delivered medications.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subcutaneous-foslevodopa-foscarbidopa-in-patients-with-advanced-parkinsons-disease-results-from-a-randomized-double-blind-double-dummy-phase-3-trial/