Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson’s Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study

作者：Jason Aldred, Eric Freire-Álvarez, А. В. Амелин, Angelo Antonini, Bruno Bergmans, Filip Bergquist, Manon Bouchard, Kumar Budur, Camille Carroll, К. Ray Chaudhuri, Susan R. Criswell, Erik Hvid Danielsen, Florin Gandor, Jia Jia, Thomas Kimber, Hideki Mochizuki, Weining Robieson, Amy M. Spiegel, David G. Standaert, Saritha Talapala, Maurizio Facheris, Victor S.C. Fung · 发表于：Neurology and Therapy · 年份：2023 · DOI：10.1007/s40120-023-00533-1 · 被引用次数：133 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Neurological disorders and treatments、Sleep and Wakefulness Research

INTRODUCTION: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. METHODS: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700-4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). RESULTS: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mo...