Objective: To compare levodopa PK, derived from ND0612 (a proprietary liquid levodopa/carbidopa formulation designed for subcutaneous (SC) administration) with Levodopa/Carbidopa Intestinal Gel (LCIG).

Background: While the efficacy of continuous levodopa infusions in managing motor complications in advanced Parkinson’s disease is well established, the requirement for invasive surgery limits the utility of current delivery systems (LCIG). ND0612 has been specifically developed as a continuous SC administered alternative for achieving steady levodopa plasma levels.

Methods: This was an open-label, cross-over study conducted in healthy subjects (aged 40-65 years). Subjects were randomized to receive 2 of 3 possible daily doses of LCIG, infused for 16 hours via a naso-jejunal tube (washout of ≥24 hours between administrations), followed by SC ND0612 infusion for 24 hours. Levodopa PK parameters (Cmax, AUC) derived from ND0612 and LCIG were compared and the relative bioavailability of levodopa from ND0612 to LCIG (reference product) was evaluated. In addition, the safety and tolerability of each route of continuous administration was assessed.

Results: Administration of comparable levodopa doses resulted in higher total plasma exposure (AUC) from ND0612 vs. LCIG indicating a higher levodopa bioavailability for ND0612. When levodopa PK parameters for ND0612 were compared against LCIG, the 90% confidence interval of the AUC and Cmax adjusted geometric mean ratios (ND0612 to LCIG) were within the range of 80-125% indicating bioequivalence. No new safety concerns were identified for ND0612.

Conclusions: Subcutaneous delivery of ND0612 achieved a comparable levodopa PK profile to a reference dose of LCIG and was shown to provide PK bioequivalence. Subcutaneous delivery of LD/CD may provide a safer alternative to direct intestinal infusion whilst providing similar clinical benefit to PD patients with motor fluctuations.  

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetic-profile-of-continuous-levodopacarbidopa-delivery-when-administered-subcutaneously-nd0612-versus-duodenal-infusion-levodopacarbidopa-intestinal-gel/