Foslevodopa/foscarbidopa Subcutaneous Infusion Maintains Similar Levodopa Exposure to Levodopa-Carbidopa Intestinal Gel Delivered to the Jejunum when Infused for 24-hours (P1-11.003)

Abstract

<h3>Objective:</h3> To compare levodopa pharmacokinetics (PK) following subcutaneous (SC) infusion of foslevodopa/foscarbidopa and jejunal delivery of Levodopa-Carbidopa Intestinal Gel (LCIG) both administered for 24 hours in healthy volunteers. <h3>Background:</h3> Treatment with LCIG offers improved symptomatic control compared to oral levodopa/carbidopa in patients with advanced Parkinson’s disease (aPD); however, it requires percutaneous endoscopic gastrostomy tube placement for jejunal delivery. Foslevodopa/foscarbidopa is an investigational drug able to provide 24-hour therapeutic levels of levodopa following SC delivery. While a previous study compared the PK of levodopa between foslevodopa/foscarbidopa and LCIG, when LCIG was administered during waking hours, the current work characterizes the levodopa PK when both the SC infusion and intestinal gel are delivered continuously for 24 hours. <h3>Design/Methods:</h3> This study was a randomized, open-label, 2-way crossover study in 20 healthy volunteers. In each period, subjects received either 24-hour foslevodopa/foscarbidopa SC infusion to the abdomen or LCIG delivered for 24 hours to the jejunum through a nasogastric tube with jejunal extension. Serial blood samples were collected to assay for levodopa concentrations. PK parameters such as area under the curve (AUC) and degree of fluctuation (DOF) were determined and compared between the two regimens. <h3>Results:</h3> Foslevodopa/foscarbidopa SC infusion provided comparable levodopa levels to LCIG over the 24-hour delivery period as assessed by the AUC and DOF parameters. From the different AUC intervals explored, the differences of the mean ranged from 1 to 8% between the foslevodopa/foscarbidopa and the LCIG regimens. Additionally, the degree of fluctuation of levodopa was similar but lower for foslevodopa/foscarbidopa compared to LCIG (mean 0.32 vs 0.50). <h3>Conclusions:</h3> Foslevodopa/foscarbidopa SC infusion delivers comparable levodopa exposure to LCIG when delivered for 24 hours. The low variability of the levodopa PK profiles supports the strategy of maintaining levodopa exposure within a narrow therapeutic window when treating motor symptoms in aPD. <b>Disclosure:</b> Dr. Rosebraugh has received personal compensation for serving as an employee of AbbVie Inc. Dr. Rosebraugh has stock in AbbVie Inc.. Dr. Facheris has received personal compensation for serving as an employee of AbbVie Inc.. Dr. Facheris has stock in AbbVie Inc..