The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program

• DOI: 10.3389/fneur.2022.1036068
• Publication Date: 2022-11-10T09:44:17Z
• Authors: Peter A. LeWitt; Fabrizio Stocchi; David Arkadir; Yoseph Caraco; Liat Adar; Itay Perlstein; Ryan Case; Nir Giladi
• Keywords: Carbidopa; Regimen

While treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated development motor complications, that correlate to fluctuating plasma concentrations, limiting its clinical utility. Continuous infusion considered be optimal delivery route for treating PD patients fluctuations, but current systems require invasive surgery. Subcutaneous (SC) has potential provide a better tolerated and more convenient continuous delivery. ND0612 in as combination product providing levodopa/carbidopa via minimally invasive, subcutaneous system experiencing response fluctuations. We present pharmacokinetic results from series studies analyzed concentrations after SC inform program.We performed six Phase I II characterize pharmacokinetics carbidopa derived with/without adjunct same ingredients. These were conducted healthy volunteers fluctuations while on their regimen.Taken together, demonstrate dose-proportionality dependent rate leading stable sustained levodopa. administered maintained near-constant, therapeutic thereby avoiding troughs are OFF time PD. The data generated this also confirmed dose ratio 8:1 would most reasonable choice development.This have demonstrated ND0612, continuously concentration 60 mg/ml combined 7.5 mg/ml, complemented levodopa/carbidopa, suitable 24 h administration achieved predict utility parenteral formulation achieving clinically useful patients.