Continuous Subcutaneous Levodopa Delivery For Parkinson'S Disease: A Randomized Study

Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson's disease (PD) experiencing motor fluctuations.Objective: 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/carbidop a 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.