Long-term safety of continuous levodopa/carbidopa infusion with ND0612: Results from the ongoing BeyoND study
Stuart Isaacson1, Tanya Simuni2, Laurence Salin3, Ryan Case3, Liat Adar3, Nissim Sasson3, Tami Yardeni3, Werner Poewe4
1Parkinson's Dis & Mov Dis Ctr of Boca Raton, 2Northwestern University Feinberg School of Medicine, 3NeuroDerm, 4Medical University Innsbruck
Objective:
To report cumulative data from the ongoing BeyoND study (NCT02726386) beyond 1 year.
Background:
Primary safety data show that subcutaneous levodopa/carbidopa infusion with ND0612 is generally safe up to 1 year of treatment. The study has been extended to 102 months, and some patients have now entered their 6th year of treatment.
Design/Methods:
This open-label safety study is conducted in PD patients (aged >30 years, Hoehn & Yahr Stage ≤3 during ON) taking ≥4 levodopa doses/day and ≥1 other PD medication and experiencing ≥2 hours of OFF time/day with predictable early-morning OFF periods. Patients were assigned to receive ND0612 for a regimen of either 16-hours/day or 24-hours/day. Patients who completed the 1-year study could continue into the extension study for up to 102 months of treatment.
Results:
Of the 214 enrolled patients, 120 completed the first year and 114 continued into the extension period. As of May 2021, 64 patients were still in the study, with a treatment duration of up to 4.6 years. The main reasons for treatment discontinuation over the whole study were infusion site reactions (ISR)/consent withdrawn due to ISR (17.7% of patients), followed by lack of efficacy (14.5%) and other treatment-emergent adverse events (TEAEs) (12.1%). Cumulative safety data showed that 73% of patients had ≥1 TEAE. Treatment-related serious adverse events occurred in 5.6% of patients. The most frequent TEAEs were ISRs such as nodules, hematoma, infection, pain, and eschar, which accounted for 486/640 related TEAEs and were generally reversible and manageable. The most common systemic TEAEs were fall (16.4%), urinary tract infection (13.1%), and nausea (10.3%).
Conclusions:
ND0612 infusion was found to be safe, with generally mild to moderate local TEAEs that were reversible and manageable. There were no major differences in safety between the 16- and 24-hour regimens. Systemic safety was typical for PD patients treated with levodopa/carbidopa.