2023 American Academy of Neurology Abstract Website

Objective:

Determine the relative bioavailability of levodopa when administered as a subcutaneous (SC) levodopa/carbidopa (LD/CD) infusion with ND0612 versus levodopa derived from oral immediate-release LD/CD (IR-LD/CD) tablets in healthy volunteers.

Background:

ND0612 is in development as the first continuous SC LD/CD delivery system for patients with Parkinson’s disease (PD) experiencing motor fluctuations. By avoiding gastrointestinal involvement, ND0612 provides increased bioavailability and reduced variability of LD/CD plasma levels. Several studies have confirmed stable, clinically relevant levodopa plasma levels following ND0612 administration.

Design/Methods:

This was a single-center, single-dose, open-label, sequence-randomized, 3-period, 2-way crossover pharmacokinetic study in 16 healthy volunteers (11M, 5F; 18-50y). Volunteers were randomized (1:1) to receive either ND0612 infused over 16h (to a total LD/CD dose of 360/45 mg) followed by oral IR-LD/CD 100/25 mg QID over 15h (given every 5h to a total dose of 400/100 mg), or vice versa with an intervening 6-day washout period.

Results:

ND0612 SC infusion reached a steady level compared to a fluctuating plasma concentration profile characterized by multiple peaks and troughs observed throughout the day with oral IR-LD/CD given QID due to the relatively short plasma half-life of levodopa. Geometric LS mean ratios [90% CI] of both AUClast and AUCinf for ND0612 compared to oral IR LD/CD were 1.30 [1.24, 1.36]. This profile resulted in a 6-fold lower levodopa fluctuation index with ND0612 vs oral IR-LD/CD.

Conclusions:

Treatment with ND0612 provides a continuous and stable levodopa level, avoiding the peaks and deep troughs associated with oral IR-LD/CD delivery. In this study, SC delivery of levodopa with ND0612 (360mg) showed a 1.3-fold higher bioavailability with a 6-fold lower fluctuation index as compared to oral IR-LD/CD delivery (400 mg).