Category: Parkinson’s Disease: Clinical Trials
Objective: To characterize safety/tolerability and pharmacokinetics (PK) of levodopa (LD) and carbidopa (CD) after delivery of foslevodopa/foscarbidopa in Parkinson’s disease (PD) patients at 4 different subcutaneous (SC) infusion sites.
Background: Foslevodopa/foscarbidopa is a soluble formulation of LD/CD prodrugs delivered as a continuous (24-hour/day) subcutaneous infusion, which provides consistent therapeutic levels of LD, mitigating the shortcomings of the progressive reduced effectiveness of oral LD. Although SC infusions are typically administered to the abdomen, patients may prefer or need to consider alternative infusion sites. The current work characterizes the LD and CD PK following foslevodopa/foscarbidopa SC infusion to arm, thigh and flank compared to the abdomen.
Method: Patients with LD-responsive PD were confined for approximately 12 days, following standardized procedures. Foslevodopa/foscarbidopa was infused consecutively in each of the designated SC sites in a 4-way randomized crossover design, 48 hours/site. Serial plasma samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. PK parameters including average concentration, degree of fluctuation and swing were compared among arm, thigh, flank and the reference abdomen SC infusion regimen.
Results: LD and CD showed similar PK based on average concentrations of arm, thigh, flank compared to the reference abdomen regimen. The coefficient of variation for average concentration ratios was similar between the sites of administration and all less than 10%. For both LD and CD, mean degree of fluctuation and mean swing values were comparable across infusion sites with 90% confidence intervals of the ratios of arm, thigh and flank over abdomen containing 1.0. Adverse events (AEs) were non-serious and mild to moderate in severity including skin related AEs with frequency and severity being similar across infusion sites.
Conclusion: Pharmacokinetics of foslevodopa/foscarbidopa is not sensitive to SC site of administration. Abdomen, arm, thigh, and flank may be suitable and interchangeable sites for SC delivery for foslevodopa/foscarbidopa.
To cite this abstract in AMA style:Y. Han, H. Kalluri, A. Jeong, C. Locke, M. Facheris, S. Gupta, M. Rosebraugh. Pharmacokinetics, Safety and Tolerability of Foslevodopa/Foscarbidopa Following Continuous Subcutaneous Infusion to Arm, Thigh and Flank compared to Abdomen in Parkinson’s Disease Patients [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/pharmacokinetics-safety-and-tolerability-of-foslevodopa-foscarbidopa-following-continuous-subcutaneous-infusion-to-arm-thigh-and-flank-compared-to-abdomen-in-parkinsons-disease-patients/. Accessed September 28, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetics-safety-and-tolerability-of-foslevodopa-foscarbidopa-following-continuous-subcutaneous-infusion-to-arm-thigh-and-flank-compared-to-abdomen-in-parkinsons-disease-patients/