Abstract Details

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.

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.

This pharmacokinetic study included 17 PD patients (Hoehn & Yahr score of ≤3 during ON & ≥2 hours daily OFF-time at baseline) who had completed at least 1-year of open-label treatment with ND0612 (16-hour or 24-hour infusion regimens). 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).

In general, increasing plasma concentrations of levodopa were associated with higher TRS Scores and more ON-time. In the 16-hour regimen, the first morning hours were characterized by a higher proportion of OFF as expected due to the low levodopa plasma concentrations, followed by more ON with non-troublesome dyskinesia until reaching clinically relevant stable levels, while the response in the 24-hour regimen showed less fluctuations over the course of the day. Levodopa pharmacokinetics and the pharmacodynamic response as assessed by the TRS were correlated.

The results of this study 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.