BouNDless: An active-controlled, randomised, double-blind, double-dummy trial of continuous subcutaneous infusion of levodopa/carbidopa with ND0612 in patients with Parkinson's disease experiencing motor complications

Background and aims: The aim of this phase 3 study (NCT04006210) is to confirm the efficacy, safety, and tolerability of continuous levodopa infusion with ND0612 in comparison to oral immediate‐release levodopa/ carbidopa in patients with Parkinson's disease (PD) experiencing motor complications. ND0612 is a proprietary drug‐device combination delivering liquid levodopa/ carbidopa (60/7.5mg/mL) via a subcutaneous (SC) infusion pump. Methods: This is a randomised, active‐controlled, parallelgroup clinical trial including two 6‐week open‐label optimisation periods followed by a 12‐week, double‐blind, double‐dummy maintenance period [Figure]. A total of 288 PD patients in Europe and the US will be enrolled (Hoehn and Yahr I‐III) to reach 202 randomised patients on ≥4 doses/day of levodopa/carbidopa oral therapy (≥400mg levodopa), experiencing ≥2.5 hours of daily OFF time. Results: The primary endpoint is the change in mean ON time without troublesome dyskinesia from Baseline to end of maintenance period (Week 12), based on patient‐reported diary assessments. Secondary outcome measures include changes in: OFF time (key secondary), UPDRS (Parts II and III), Patient's and Clinician's Global Impressions of Change, ON time without dyskinesia, PDQ‐39 and Parkinson's Disease Sleep Scale scores. Clinical assessments will be conducted by a blinded rater. Safety and tolerability will be assessed via adverse event reporting, including local skin safety assessment, rates of premature discontinuation, and treatment compliance. Conclusion: BouNDless will be the 1st phase 3 randomized, active‐controlled trial to evaluate the efficacy and safety of continuous subcutaneous levodopa/carbidopa delivery with ND0612 compared to oral immediate‐release levodopa/ carbidopa in patients with PD experiencing motor fluctuations. (Figure Presented).