Objective: To 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.
Method: 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. This profile resulted in a 6-fold lower levodopa fluctuation index with ND0612 vs oral IR-LD/CD. Compared with oral IR-LD/CD, levodopa dose-normalized AUCs for ND0612 were approximately 1.3-fold higher.
Conclusion: These PK data confirm that treatment with ND0612 provides a continuous and stable levodopa level, avoiding the peaks and deep troughs associated with oral IR-LD/CD delivery. Levodopa bioavailability (based on dose normalized AUCs) was higher with ND0612 compared to orally administered IR-LD/CD. Therefore, it may be possible to increase the total levodopa dose (from ND0612 and oral) and potentially decrease OFF time in fluctuating PD patients, without increasing troublesome dyskinesia.
To cite this abstract in AMA style:
L. Adar, N. Vostokova. Relative bioavailability of levodopa administered as a subcutaneous infusion with ND0612 versus oral immediate-release levodopa/carbidopa tablets [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/relative-bioavailability-of-levodopa-administered-as-a-subcutaneous-infusion-with-nd0612-versus-oral-immediate-release-levodopa-carbidopa-tablets/. Accessed September 7, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/relative-bioavailability-of-levodopa-administered-as-a-subcutaneous-infusion-with-nd0612-versus-oral-immediate-release-levodopa-carbidopa-tablets/