Continuous subcutaneous infusion linked to more ‘on’ time in Parkinson’s

Key takeaways:

• The study examined efficacy of subcutaneous vs. oral administration of carbidopa/levodopa.
• Subcutaneous infusion provided nearly 2 more hours per day of ‘on’ time without dyskinesia.

Compared with oral administration, continuous subcutaneous infusion of carbidopa/levodopa was linked to nearly 2 more hours of “on” time without dyskinesia in adults with Parkinson’s disease, data from The Lancet Neurology show.

“While oral levodopa is the primary treatment for [Parkinson’s disease], the benefits become shorter per dose, leading to motor fluctuations and dyskinesia despite changes in dose and frequency,” Alberto J. Espay, MD, MSc, principal study investigator and director of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati, told Healio in an email.

To examine the benefits of continuous infusion treatments as a buffer against dyskinesia, Espay and colleagues conducted a phase 3, randomized, double-blind, double-dummy, active-controlled clinical trial at 117 academic and community neurology sites in 16 countries.

From an initial cohort of 381 individuals, the analysis included 259 adults diagnosed with PD who experienced at least 2.5 hours per day of “off” time. All participants underwent an open-label run-in phase of less than 12 weeks, during which optimal regimens were established for both oral immediate-release levodopa–carbidopa (LD/CD) and for 24 hour-a-day subcutaneous ND0612 infusion (levodopa–carbidopa 60/7.5 mg/mL), with supplemental oral LD/CD if needed. Participants were randomized 1:1 to 12 weeks of double-blind treatment with their optimized regimen of either subcutaneous ND0612 or oral LD/CD with matching oral or subcutaneous placebo as required. A total of 243 participants completed the study.

The primary efficacy endpoint was the change from baseline to end of the double-blind phase in total daily “on” time without troublesome dyskinesia, analyzed by intention to treat.

According to results, treatment with subcutaneous ND0612 provided an additional 1.72 hours (95% CI, 1.08-2.36) of “on” time without troublesome dyskinesia compared with oral LD/CD (change from baseline of –0.48 h [–0.94 to –0.02] with subcutaneous ND0612 vs. –2.20 h [–2.65 to –1.74] with oral LD/CD).

Adverse events were reported by a majority of participants in both treatment groups, with the most common being mild infusion-site reactions during the open-label and double-blind phases. Serious adverse events occurred in four participants in the ND0612 group, related to study treatment as well as paresthesia and peripheral sensorimotor neuropathy. One death was recorded in the ND0612 group double-blind phase, but unrelated to study treatment, the researchers wrote.

“These findings show us the beneficial impact that continuous, subcutaneous delivery of levodopa/carbidopa with ND0612 may have on people with PD experiencing motor fluctuations, which can be unpredictable and take a toll on patients’ physical and emotional health,” Espay told Healio.