Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021;11(1):177-186.
doi: 10.3233/JPD-202285.

Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study

C Warren Olanow  1   2 , Alberto J Espay  3 , Fabrizio Stocchi  4 , Aaron L Ellenbogen  5   6 , Mika Leinonen  1   7 , Liat Adar  8 , Ryan J Case  8 , Shir Fuchs Orenbach  8 , Tami Yardeni  8 , Sheila Oren  8 , Werner Poewe  9 ; 006 study group
Affiliations
Randomized Controlled Trial

Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study

C Warren Olanow et al. J Parkinsons Dis. 2021.

Abstract

Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson's disease (PD) experiencing motor fluctuationsObjective:Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD.

Methods: This was a 28-day open-label study (NCT02577523) in PD patients with ≥2.5 hours/day of OFF time despite optimized treatment. Patients were randomized to treatment with either a 24-hour infusion (levodopa/carbidopa dose of 720/90 mg) or a 14-hour 'waking-day' infusion (levodopa/carbidopa dose of 538/68 mg plus a morning oral dose of 150/15 mg). Supplemental oral doses of levodopa were permitted for patients in both groups if required. In-clinic assessments of OFF time (primary endpoint) and ON time with or without dyskinesia were determined by a blinded rater over 8 hours (normalized to 16 hours).

Results: A total of 38 patients were randomized and 33 (87%) completed the study. Compared to baseline, OFF time for the overall population was reduced by a least squares (LS) mean[95% CI] of 2.0[- 3.3, - 0.7] hours (p = 0.003). ON time with no/mild dyskinesia (no troublesome dyskinesia) was increased from baseline by a LS mean of 3.3[2.0, 4.6] hours (p < 0.0001), and ON time with moderate/severe dyskinesia was reduced by a LS mean of 1.2[- 1.8, - 0.5] hours (p≤0.001). Reduction in OFF time was larger in the 24-hour group (- 2.8[- 4.6, - 0.9] hours; p = 0.004) than in the 14-hour group (- 1.3[- 3.1, 0.5] hours; p = 0.16). Complete resolution of OFF time was observed in 42% (n = 8) of patients in the 24-hour group. Infusion site reactions were the most common adverse event.

Conclusion: This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.

Keywords: Motor fluctuations; ND0612; Parkinson’s disease; subcutaneous levodopa infusion.

PubMed Disclaimer

Conflict of interest statement

This study was sponsored by NeuroDerm Ltd. C. Warren Olanow has stock ownership in Clintrex which was contracted by NeuroDerm to provide services for this study. Alberto J. Espay, Fabrizio Stocchi, Aaron Ellenbogen and Werner Poewe were all investigators in the 006 study and report fees for consultancy from NeuroDerm Ltd. Mika Leinonen reports consultancy for Clintrex LLC. Liat Adar, Ryan Case, Shir Fuchs Orenbach, Tami Yardeni and Sheila Oren are employed by NeuroDerm Ltd.

Figures

Fig. 1
Fig. 1
Study flow.
Fig. 2
Fig. 2
Changes in ON and OFF time after 28 days ND0612 infusion.
See this image and copyright information in PMC

References

    1. Ahlskog JE, Muenter MD (2001) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 16, 448–458. - PubMed
    1. Hely MA, Morris JG, Traficante R, Reid WG, O’Sullivan DJ, Williamson PM (1999) The Sydney multicentre study of Parkinson’s disease: Progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 67, 300448–307. - PMC - PubMed
    1. Olanow CW, Kieburtz K, Rascol O, Poewe W, Schapira AH, Emre M, Nissinen H, Leinonen M, Stocchi F, Stalevo Reduction in Dyskinesia Evaluation in Parkinson’s Disease (STRIDE-PD) Investigators (2013) Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord 28, 1064–1071. - PubMed
    1. Chapuis S, Ouchchane L, Metz O, Gerbaud L, Durif F (2005) Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord 20, 224–230. - PubMed
    1. Hechtner MC, Vogt T, Zollner Y, Schroder S, Sauer JB, Binder H, Singer S, Mikolajczyk R (2014) Quality of life in Parkinson’s disease patients with motor fluctuations and dyskinesias in five European countries. Parkinsonism Relat Disord 20, 969–974. - PubMed

Publication types

MeSH terms