Subcutaneous levodopa (L-dopa)/carbidopa (C-dopa) continuous infusion with ND0612, an investigational subcutaneous delivery system providing minimally invasive continuous infusion, is a safe treatment option for patients with Parkinson disease (PD), according to study results published in Movement Disorders.
Previous studies supported the efficacy of ND0612, with data showing stable plasma L-dopa concentrations, reduction in daily OFF time and increase ON time. The BeyoND study is an ongoing, international, multicenter, open-label study, initiated in May 2016. The objective of the current study was to determine the long-term safety and tolerability of 2 ND0612 dosing regimens over 12 months in patients with PD and motor fluctuations.
Of the 276 patients screened, the study sample included 214 participants from 46 sites in 8 countries, including 90 patients (mean age, 64.2 years; 64.4% men) assigned to the 24-hour regimen and 124 patients (mean age, 63.9 years; 67.7% men) assigned to 16-hour regimen. Overall, 127 patients completed 12 months in the study.
Consent withdrawal (19.6%) and adverse events (17.3%) were the most common causes for study discontinuation. Concomitant catechol-O-methyltransferase inhibitor use was associated with lower rates of discontinuation (odds ratio, 0.43, P =.01), and baseline body mass index <20 was associated with higher rates of discontinuation (odds ratio, 3.15, P =.03).
Rates of discontinuation decreased from 49% to 29% for patients enrolled after a March 2018 protocol amendment in response to a higher than expected study dropout rate, and with increased site training on infusion site reactions.
Over 1 year, 85.5% of patients reported ≥1 treatment-associated adverse events, most were mild-moderate in severity, without major differences between the 2 dosing regimens. Of 37 patients (17.3%) who terminated treatment prematurely due to adverse events, 22 (10.3%) did so due to infusion site reactions, especially skin nodules and hematomas. Infusion site infection was more common in the 24-hour than 16-hour dosing regimen (16.7% vs. 8.1%, respectively).
Serious treatment-associated adverse events were observed in 31 patients (14.5%), with a similar incidence in both study groups. Infusion site reaction (5 patients), ON-OFF phenomenon (3 patients), and rib fracture (2 patients) were the most common serious adverse events.
The study had several limitations, including the open-label design and a higher than expected dropout rate.
“Subcutaneous levodopa/carbidopa continuous infusion with ND0612 is generally safe, with typical infusion site reactions for SC [subcutaneous] delivery as the main adverse event,” concluded the researchers.
Disclosure: This research was supported by NeuroDerm Ltd. Please see the original reference for a full list of disclosures.
Poewe W, Stocchi F, Arkadir D, et al. Subcutaneous levodopa infusion for Parkinson’s disease: 1-year data from the open-label BeyoND Study. Mov Disord. Published online Sep 8, 2021. doi: 10.1002/mds.28758