ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study

Nir Giladi*, Tanya Gurevich, Ruth Djaldetti, Liat Adar, Ryan Case, Shelly Leibman-Barak, Nissim Sasson, Yoseph Caraco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations. Methods: This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC. During Period-2, 16 patients were randomized to receive 7 days treatment with ND0612 or ND0612 plus oral entacapone. Reduction in OFF time was analyzed as an exploratory measure using a futility design with a predefined margin of 1.6 h. Results: ND0612 was well-tolerated; most patients experienced infusion site nodules (95% vs. 56% with placebo), which all resolved without sequelae. Patients treated with adjunct ND0612 during Period-1 avoided deep troughs in levodopa plasma levels and had a decreased fluctuation index versus placebo (1.6 ± 0.5 vs 3.1 ± 1.6 at end of Period-1, respectively). In Period-2, the coadministration of entacapone with continuous ND0612 SC infusion translated to an increase in mean levodopa AUC0–10h compared to baseline. Exploratory efficacy analysis of Period 1 showed mean ± SD OFF time reductions of −2.13 ± 2.24 [90%CI: -2.8, ∞] hours (p = 0.84 using H0 of μ0 ≤-1.6). Conclusion: Levodopa/carbidopa infusion with ND0612 was generally well-tolerated and resulted in reduced fluctuations in plasma levodopa concentrations when given with SoC oral levodopa. ND0612 met the efficacy endpoint for the futility design.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalParkinsonism and Related Disorders
Volume91
DOIs
StatePublished - Oct 2021

Funding

FundersFunder number
Aufzien Academic Center in Tel-Aviv University
Medison
Medison and Allergan
NeuroDerm
NeuroDerm, Ltd
Sanofi-Genzyme and Biogen
Sieratzki Family Foundation
Michael J. Fox Foundation for Parkinson's Research
National Parkinson Foundation
Medtronic
Teva Pharmaceutical Industries
AbbVie
Allergan
International Parkinson and Movement Disorder Society
Parkinson's Foundation
European Commission
Israel Science Foundation
Tel Aviv University

    Keywords

    • Infusion
    • Levodopa
    • Motor fluctuations
    • ND0612
    • Parkinson's disease
    • Pharmacokinetics

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