Long-term Safety and Tolerability of Foslevodopa/Foscarbidopa for Treatment of Motor Fluctuations in Parkinson’s Disease
Victor Fung1, Filip Bergquist2, Sara Dhanani3, Maurizio Facheris4, Florin Gandor5, Stuart Isaacson6, Anna Jeong4, Jia Jia4, Amy Spiegel4, Jason Aldred7
1Department of Neurology, Westmead Hospital, Sydney, NSW, Australia and Sydney Medical School, Sydney, NSW, Australia, 2Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden and Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden, 3Banner Sun Health Research Institute, Sun City, AZ, USA, 4AbbVie Inc., North Chicago, IL, USA, 5Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany and Movement Disorders Hospital, Beelitz-Heilstätten, Germany, 6Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA, 7Selkirk Neurology and Inland Northwest Research, Spokane, WA, USA
Objective:
A phase 3 open-label extension study (OLES) to evaluate long-term safety/tolerability of continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa (LDp/CDp) in patients with Parkinson’s disease (PD).
Background:
LDp/CDp is a soluble formulation of levodopa (LD)/carbidopa prodrugs delivered as a 24-hour/day CSCI for the treatment of motor fluctuations in PD. LDp/CDp demonstrated a favorable risk/benefit profile in a 52-week, open-label phase 3 study (NCT03781167); patients who completed the parent trial could enroll in the OLES (NCT04379050).
Design/Methods:
LD-responsive PD patients with inadequately controlled (≥2.5 hours “Off” time/day) motor symptoms were enrolled in the parent study and continued into the ongoing OLES. LDp/CDp infusions are individually optimized (600–4250 mg LD equivalents/24 hours). Safety/tolerability is the primary endpoint. Key secondary endpoints include change from OLES baseline for mean normalized daily “Off” and “On” times, morning akinesia (“Off” upon awakening), and quality of life (QoL) scores (PDQ-39 and EQ-5D-5L). Efficacy data are presented through Week 84 (interim data cutoff August 17,2022).
Results:
A total of 129 (94.2%) patients enrolled in the OLES and few have discontinued (16 [12.4%]). Mean (SD) and maximum exposure duration are 470.1(386.9) and 1169 days, respectively. Overall, 83.7% of patients experienced ≥1 AE; most were non-serious and mild/moderate in severity. “On” and “Off” times were generally stable from entry into the OLES through Week 84 (change from OLES baseline in “On” time without troublesome dyskinesia: −0.6[2.9] hours, P=.252; “On” time with troublesome dyskinesia: −0.2[1.2] hours, P=.364; “Off” time: 0.9[2.7] hours, P=.102). Most patients (75%) reported awakening in the “On” state (n/N=15/20) at Week 84. The improvement in the parent study on PDQ-39 and EQ-5D-5L scores was maintained from OLES baseline to Week 72.
Conclusions:
Long-term LDp/CDp was generally safe and well tolerated. Treatment-related improvements in motor fluctuations, morning akinesia, and QoL observed at the conclusion of the 52-week parent study were maintained throughout the OLES.