Objective: To evaluate the pharmacokinetic–pharmacodynamic relationships between levodopa plasma exposure and motor treatment response in patients with Parkinson’s disease (PD) treated with ND0612 and adjunct oral PD medication.

Background: ND0612 is an investigational subcutaneous delivery system providing minimally invasive, continuous infusion of liquid levodopa/carbidopa under development for potential sustained relief of motor fluctuations in patients with PD.

Method: The BeyoND study is an ongoing international, open-label study (NCT02726386) evaluating the long-term safety of two ND0612 dosing regimens in patients with PD (Hoehn & Yahr score of ≤3 during ON) and experiencing motor fluctuations (≥2 hours daily OFF-time). The pharmacokinetic substudy included 17 patients treated with ND0612 who had completed at least 1-year of treatment. In parallel to the pharmacokinetic parameters (assessed over 24 hours), the pharmacodynamic response was assessed using the treatment response scale (TRS) and patient ON/OFF diaries (30-minute intervals over 24 hours).

Results: In general, increasing plasma concentrations of levodopa were associated with higher TRS
Scores and more ON-time. Ratings of individual motor signs (finger tap, hand pronate/supinate, and arising from chair) were stable over the course of a day. A trend toward lower bradykinesia and hypokinesia scores was also observed with increasing levodopa concentrations. Levodopa pharmacokinetics and the pharmacodynamic response as assessed by the TRS were correlated.

Conclusion: The results of this substudy support the translation of stable levodopa pharmacokinetics, as provided by continuous infusion with ND0612, into stable and improved motor responses in PD patients experiencing motor fluctuations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetic-pharmacodynamics-of-levodopa-carbidopa-following-subcutaneous-infusion-with-nd0612-results-from-the-beyond-pharmacokinetic-substudy/