Category: Parkinson’s Disease: Clinical Trials
Objective: Determine the efficacy, safety, and tolerability of ND0612 versus oral immediate-release levodopa/carbidopa (IR-LD/CD) in people with Parkinson’s disease (PwP) experiencing motor fluctuations.
Background: ND0612 is an investigational, continuous 24-hours/day subcutaneous infusion of LD/CD.
Method: This is a phase 3, double-blind, double-dummy (DBDD), parallel-group 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 then 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 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maintained in the ND0612 group (11.5h at endpoint), but decreased in the IR-LD/CD group who had their ND0612 infusion withdrawn (9.8h at endpoint). Thus, the study met its primary endpoint, with the ND0612 regimen providing an additional 1.72h [95%CI: 1.08h, 2.36h] of ON-time without troublesome dyskinesia 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 (84.2% during open-label conversion to infusion, during the DBDD period the rates were 57.0% for ND0612 vs. 43.5% 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.
Conclusion: In this study, treatment with ND0612 led to clinically meaningful improvement in motor fluctuations and functional endpoints, such as improved motor experiences of daily living, vs oral IR-LD/CD and was generally well tolerated.
To cite this abstract in AMA style:O. Rascol, A. Albanese, A. Ellenbogen, J. Ferreira, N. Giladi, T. Gurevich, S. Hassin-Baer, J. Hernandez-Vara, S. Isaacson, K. Kieburtz, P. Lewitt, L. Lopez-Manzanares, CW. Olanow, R. Pahwa, W. Poewe, H. Sarva, F. Stocchi, T. Yardeni, L. Adar, L. Salin, N. Lopes, N. Sasson, R. Case, A. Espay. Continuous subcutaneous levodopa/carbidopa infusion with ND0612 for patients with Parkinson’s disease and motor fluctuations: Results from the Phase 3 randomized, active-controlled BouNDless study [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/continuous-subcutaneous-levodopa-carbidopa-infusion-with-nd0612-for-patients-with-parkinsons-disease-and-motor-fluctuations-results-from-the-phase-3-randomized-active-controlled-boundless-s/. Accessed September 28, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/continuous-subcutaneous-levodopa-carbidopa-infusion-with-nd0612-for-patients-with-parkinsons-disease-and-motor-fluctuations-results-from-the-phase-3-randomized-active-controlled-boundless-s/