Continuous subcutaneous levodopa/carbidopa infusion (ND0612) for patients with Parkinson’s disease and motor fluctuations: A Phase 3, active-controlled study (BouNDless)
Recommended Citation
Stocchi F, Espay A, Albanese A, Ellenbogen A, Ferreira JJ, Giladi N, Gurevich T, Hassin-Baer S, Hernandez-Vara J, Isaacson S, Kieburtz K, LeWitt P, Lopez-Manzanares L, Olanow CW, Pahwa R, Poewe W, Sarva H, Yardeni T, Adar L, Lopes N, Sasson N, Case R, and Rascol O. Continuous subcutaneous levodopa/carbidopa infusion (ND0612) for patients with Parkinson's disease and motor fluctuations: A Phase 3, active-controlled study (BouNDless). Parkinsonism and Related Disorders 2024; 122.
Document Type
Conference Proceeding
Publication Date
5-1-2024
Publication Title
Parkinsonism and Related Disorders
Abstract
Background: We determined the efficacy, safety, and tolerability of ND0612, an investigational, continuous 24-hours/day subcutaneous infusion of levodopa/carbidopa (LD/CD), versus oral immediate-release (IR) LD/CD in people with Parkinson’s disease (PwP) experiencing motor fluctuations.
Methods: This is a phase 3, double-blind, double-dummy (DBDD) trial (NCT04006210). PwP on ≥4 oral LD/CD doses/day (≥400mg/day LD) and experiencing ≥2.5h of daily OFF-time underwent 4-6 weeks of open-label IR-LD/CD dose adjustment followed by 4-6 weeks of open-label ND0612 conversion (+ IR-LD/CD as needed). Patients were randomized (1:1) to 12-week DBDD treatment with either their optimized ND0612 or IR-LD/CD regimens.
Results: In the open-label adjustment/conversion phases, mean ON-time without troublesome dyskinesia (OTwoTD) increased from 9.4h (both arms) at enrollment to 11.8h (ND0612) and 12.1h (IR-LD/CD) following optimization of the ND0612 regimen. During the 12-week DBDD treatment OTwoTD was maintained in the ND0612 group (11.5h at endpoint) but decreased in the IR-LD/CD group who had their ND0612 infusion withdrawn (9.8h at endpoint). The study met its primary endpoint, with the ND0612 regimen providing an additional 1.72h [95%CI: 1.08h, 2.36h] of OTwoTD compared with IR-LD/CD (p<0.0001). Significant treatment effects (TE) vs. IR-LD/CD were also seen in the hierarchical secondary endpoints: OFF-time (TE: -1.40 [-1.99, -0.80]h, p<0.0001), MDS-UPDRS Part II (TE: -3.05 [-4.28, -1.81], p<0.0001) and global impressions by patients (Odds ratio [OR] of improvement: 5.31 [2.67, 10.58], p<0.0001) and clinicians (OR: 7.23 [3.57, 14.64], p<0.0001). Infusion site reactions were the most reported adverse events (82.6% during open-label conversion to infusion, during the DBDD period the rates were 57.0% for ND0612 vs. 42.7% for IR-LD/CD). Discontinuation rates after randomization (DBDD phase; ND0612 vs IR-LD/CD) were 6.3% vs 6.1% overall, and 5.5% vs 3.1% due to adverse events.
Conclusions: ND0612 treatment led to clinically meaningful improvement in motor fluctuations and functional endpoints vs oral IR-LD/CD and was generally well tolerated.
Volume
122
First Page
106149
