Improvement of “On” and “Off” Times in Patients with Advanced Parkinson’s Disease Treated with Foslevodopa/Foscarbidopa: Subgroup Analyses from a Phase 3 Randomized Study
Drew Kern1, Robert Hauser2, Thomas Kimber3, Okeanis Vaou4, Lars Bergmann5, Resmi Gupta5, Anna Jeong5, Jia Jia5, Megha Shah5, Michael Soileau6
1University of Colorado Anschutz Medical Campus, 2University of South Florida Parkinson’s Disease and Movement Disorders Center of Excellence, 3Royal Adelaide Hospital, 4Steward Medical Group, St. Elizabeth’s Medical Center, 5AbbVie Inc., 6Texas Movement Disorder Specialists
Objective:
To compare the efficacy of subcutaneous foslevodopa/foscarbidopa (LDP/CDP) with oral levodopa/carbidopa (LD/CD) across prespecified subgroups of patients with advanced Parkinson’s disease (PD) in a phase 3 study.
Background:
As PD progresses, motor fluctuations and dyskinesias become more challenging to control with oral levodopa. LDP/CDP is a new, soluble formulation of LD/CD prodrugs delivered as a 24-hour/day continuous subcutaneous infusion. In a phase 3 study, LDP/CDP significantly increased “On” time and reduced “Off” time vs oral LD/CD.
Design/Methods:
A prespecified subgroup analysis was conducted in patients with advanced PD from a phase 3, randomized, double-blind, active-controlled study (NCT04380142) who received LDP/CDP or oral LD/CD for 12 weeks. The change from baseline to final visit in “On” time without dyskinesia, “On” time without troublesome dyskinesia, and “Off” time were evaluated in patient subgroups: age (<65 or ≥65 years), sex, race (White or other), country (United States or Australia), PD duration (<10 or ≥10 years), and concomitant dopamine agonist use. “On” and “Off” times were normalized to a 16-hour waking day and summarized by least squares means (LSM) calculated through analysis of covariance.
Results:
This analysis included 139 patients (LDP/CDP, N=73; oral LD/CD, N=66). Patients aged <65 years receiving LDP/CDP compared with oral LD/CD showed significant improvement from baseline to last evaluation in “On” time without troublesome dyskinesia (LSM [SE] 3.5 [0.7] hours vs 0.5 [0.7] hours; P=.003); patients aged ≥65 years showed numerical improvements (1.7 [0.5] hours vs 1.0 [0.5] hours). In all other subgroups, patients receiving LDP/CDP compared with oral LD/CD showed greater numerical improvements in “On” time without dyskinesia, “On” time without troublesome dyskinesia, and “Off” time. No significant differences in treatment effects were observed between any of the subgroups.
Conclusions:
Patients experienced greater benefits with LDP/CDP vs oral LD/CD across all subgroups. No significant differences in treatment response were evident in any subgroup.