Safety of Foslevodopa/Foscarbidopa During Optimization and Maintenance Treatment: Post Hoc Analysis of a Phase 3 Trial
Drew Kern1, Khashayar Dashtipour2, Jason Aldred3, Thomas Kimber4, Robert Iansek5, Pavnit Kukreja6, Lars Bergmann6, Nahome Fisseha6, Resmi Gupta6, Saritha Talapala6, Anna Jeong6, Victor Fung7, Vincent Lepetit1
1Department of Neurology and Neurosurgery, University of Colorado Anschutz Medical Campus, 2Loma Linda University, 3Selkirk Neurology & Inland Northwest Research, 4Department of Neurology Unit, Royal Adelaide Hospital; Faculty of Health and Medical Sciences, University of Adelaide, 5Kingston Centre, Monash Health, 6AbbVie Inc., 7Movement Disorders Unit, Westmead Hospital; Sydney Medical School, University of Sydney
Objective:
To characterize the time course of adverse events (AEs) in patients with Parkinson’s disease (PD) and motor fluctuation treated with foslevodopa/foscarbidopa.
Background:
Continuous subcutaneous infusion with foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs, provides individualized, 24-hour/day therapy.
Design/Methods:
Patients aged ≥30 years with idiopathic, LD-responsive PD inadequately controlled with current therapy (≥2.5 average “Off” hours/day) were enrolled in a 12-week, phase 3, randomized, double-blind study comparing foslevodopa/foscarbidopa to oral immediate release LD/CD (NCT04380142). Foslevodopa/foscarbidopa doses were titrated and individualized during the 4-week optimization period, followed by a stable dose regimen during the 8-week maintenance period. Safety was assessed in all patients who received ≥1 dose of study drug.
Results:
A total of 74 patients received foslevodopa/foscarbidopa. Overall AEs occurred more frequently during the 4-week optimization vs the 8-week maintenance period (74.3% vs 67.9%), as did treatment discontinuations due to AEs (16.2% vs 7.1%). A greater proportion of patients experienced movement-related AEs during optimization vs maintenance, including dyskinesia (10.8% vs 0%), “On” and “Off” phenomenon (6.8% vs 1.8%), and falls (13.5% vs 8.9%). Incidence of infusion site AEs was higher during optimization vs maintenance (67.6% vs 58.9%); individual infusion site AEs generally followed a similar trend (erythema [20.3% vs 21.4%], pain [21.6% vs 8.9%], cellulitis [10.8% vs 12.5%], bruising [6.8% vs 1.8%], nodules [5.4% vs 3.6%]).
Conclusions:
In this phase 3 trial involving patients with PD treated with foslevodopa/foscarbidopa, AEs and discontinuations were generally higher during the 4-week optimization compared with the 8-week maintenance period. Higher rates of AEs and discontinuations during optimization may have been the result of the dose titration process and acclimation to a new drug delivery system. Patient and physician training, education, and expectation setting before treatment initiation and during optimization may help reduce rates of treatment discontinuation.