Pharmacokinetic and safety characterisation of carbidopa/levodopa subcutaneous infusion (ND0612): Phase I studies in healthy volunteers and patients with fluctuating Parkinson's disease
Lewitt P, Caraco Y, Adar L, and Oren S. Pharmacokinetic and safety characterisation of carbidopa/levodopa subcutaneous infusion (ND0612): Phase I studies in healthy volunteers and patients with fluctuating Parkinson's disease. Eur J Neurol 2018; 25(Suppl 2):514.
Eur J Neurol
Background and aims: Improving the continuity of carbidopa/levodopa (CD/LD) delivery is desirable in Parkinson's disease (PD) patients experiencing motor fluctuations. As an alternative to oral LD formulations with pulsatile pharmacokinetics, ND0612 is under development as a drug-device combination to provide continuous delivery of CD/LD (without the need for surgical gastrostomy tube implantation for drug infusion). Methods: Study 001 was a dose-escalating study conducted in healthy volunteers (n=54). Study 002 was a randomised, cross-over study in 8 PD patients experiencing motor fluctuations; both treatments (placebo/ND0612) were given with 2 doses of Stalevo® 100. CD/LD plasma concentrations at steady-state were assessed following continuous ND0612 subcutaneous delivery over 24 hours. Systemic and local skin safety were evaluated. Results: Study 001: LD and CD plasma concentrations increased proportionally as a function of ND0612 infusion rate during testing of low (night-rate of 80μl/h) and a high (day-rate of 240 μl/h) delivery. Study 002: In PD patients, ND0612 demonstrated plasma concentrations that were markedly increased in the therapeutic range and steadystate plasma LD concentrations with substantially reduced (10-fold) fluctuations in LD plasma concentrations. In both studies, ND0612 showed good systemic tolerability. For some subjects, small, transient nodules were palpable at infusion sites. Conclusion: Subcutaneous delivery of ND0612 in PD patients can achieve continuous therapeutic LD plasma concentrations, offering the potential for fewer motor fluctuations.