biostudies-literatureUnknown11(1)Olanow CW<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.Journal of Parkinson's disease177-186https://www.ebi.ac.uk/biostudies/studies/S-EPMC7990424biostudies-literatureContinuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study.PMC7990424Yardeni T006 study groupCase RJOlanow CWEspay AJOrenbach SFPoewe WAdar LStocchi FOren SEllenbogen ALLeinonen MfalseContinuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study.<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.2021-01-01T00:00:00Z20212024-11-21T08:11:43.788Z2022-02-09T15:00:42.002ZS-EPMC79904243316494510.3233/JPD-202285