Determine the efficacy, safety, and tolerability of ND0612 versus oral immediate-release levodopa/carbidopa (IR-LD/CD) in patients with Parkinson’s disease (PwP) experiencing motor fluctuations.

ND0612 is an investigational, continuous 24-hours/day subcutaneous infusion of levodopa/carbidopa.

Double-blind, double-dummy (DBDD), parallel-group clinical 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 with adjunctive oral IR-LD/CD as needed to optimize ND0612 regimens. Patients were then randomized (1:1) to 12-week DBDD treatment with either their optimized ND0612 or IR-LD/CD regimens. Primary efficacy endpoint was the change in ON-time without troublesome dyskinesia from self-report diaries.

Baseline characteristics of the 259 patients were balanced between groups. In the DBDD, the ND0612 regimen provided an additional 1.72h [1.08h, 2.36h] of ON-time without troublesome dyskinesia compared to IR-LD/CD (p<0.0001). Mean ON-time without troublesome dyskinesia increased in both arms while on ND0612 during conversion from 9.4h (both arms) at enrollment to 11.8h (ND0612) and 12.1h (IR-LD/CD). During the 12-week DBDD treatment, ON-time without troublesome dyskinesia was maintained in the ND0612 group (11.5h at endpoint) but decreased in the IR-LD/CD group (9.9h at endpoint). Significant treatment effects were also seen in the first four hierarchical secondary endpoints: OFF-time, MDS-UPDRS Part II, and global impressions by patients and clinicians (all p<0.0001). Infusion site reactions were the most reported adverse events (83.8% during conversion, DBDD: 57.0% for ND0612, 42.7% for IR-LD/CD). Discontinuation rates overall and due to adverse events in DBDD were 6.3% and 5.5% for the ND0612 group and 6.1% and 3.1% for the IR-LD/CD groups.

In this study, treatment with ND0612 led to significant, clinically meaningful improvement in motor fluctuations and functional endpoints such as improved experiences of daily living vs oral IR-LD/CD and was well tolerated.