Favorable Results Reported for New Levodopa/Carbidopa Infusion for Parkinson Disease

In the phase 3 BouNDless trial (NCT04006210), continuous, 24 hour/day subcutaneous infusion of levodopa/carbidopa (LD/CD) (ND0612; Neuroderm, Rehovot, Israel) for individuals with Parkinson disease (PD) and motor fluctuations had a statistically significant difference (P<.0001) of 1.72 hours in "ON" time without dyskinesia. “ON” time is a term used to describe periods in which medication is working to control both motor and nonmotor symptoms in those with PD.

The multicenter, active-controlled, randomized, double-blind, double-dummy (DBDD) phase 3 trial demonstrated superiority in the primary endpoint, defined as a change from baseline (start of infusion) to end of the maintenance period in mean ON time without dyskinesia, normalized to 16 waking hours, using patient-rated ON/OFF diary assessments. Participants were randomized to receive infusion LD/CD or oral LD/CD for a 12-week DBDD period after the 2 sequential open-label optimization periods. 

The trial also demonstrated superior efficacy in secondary endpoints including measured OFF time, MDS-Unified Parkinson Disease Rating Scale Part 2 score (MDS-UPDRS motor experiences of daily living sub-score) (P<0.0001), the Patient Global Impression of Change (PGIC) (P<0.0001), and the Clinical Global Impression of Improvement (CGI-I) (P<0.0001).

"With these positive results for the primary endpoint and 4 secondary endpoints, ND0612 has confirmed its potential as an effective treatment strategy for PD patients with motor fluctuations, despite optimization of oral therapies," said professor Alberto Espay, MD, FAAN, Primary US Investigator of BouNDless and Director of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati. "Continuous subcutaneous LD/CD treatment shows promise to change the treatment paradigm and transform the lives of patients with Parkinson’s disease."  

Reported adverse reactions were typical of those in the safety profile of oral LD/CD. Infusion site reactions (hematoma, infection, and erythema) were reported more frequently in infusion LD/CD participants. The "on and off phenomenon" falls were reported less frequently in the infusion LD/CD group compared with the oral LD/CD group.  Discontinuation in the infusion LD/CD group was 6.3% of participants during the DBDD period compared with 6.1% of participants in the oral LD/CD group. Adverse events contributed to 5.5% of the discontinuations in the infusion group compared with 3.1% in the oral LD/CD group.