Continuous subcutaneous foslevodopa-foscarbidopa improves motor symptoms in advanced PD

Continuous subcutaneous foslevodopa-foscarbidopa improved motor symptoms and reduced motor fluctuations compared with oral levodopa-carbidopa in patients with advanced Parkinson’s disease, according to a study in The Lancet Neurology.

“Most patients with Parkinson’s disease respond well to oral levodopa initially; however, its effectiveness diminishes over time,” Michael J. Soileau, MD, of the Texas Movement Disorder Specialists, and colleagues wrote. “A significant, unmet need exists for patients with advanced Parkinson’s disease to have an individualized, continuous and nonsurgical therapy that provides symptomatic relief via the predictable delivery of levodopa.”

Researchers sought to assess the safety and efficacy of continuous subcutaneous infusion of foslevodopa-foscarbidopa in inadequately controlled, levodopa-responsive patients with advanced PD. Participants, aged at least 30 years, were required to have an average off time of at least 2.5 hours per day over 3 consecutive days.

Researchers initiated a 12-week randomized, double-blind, double-dummy, active-controlled study at 65 academic and community study centers in the United States and Australia. Of 270 screened participants, 141 were randomly assigned to receive continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n = 74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n = 67).

The primary and secondary endpoints were change from baseline to week 12 in on time without troublesome dyskinesia and off time, respectively. Safety and tolerability also were evaluated throughout the trial.

Compared with levodopa-carbidopa, foslevodopa-foscarbidopa demonstrated a significantly greater increase in on time without troublesome dyskinesia (2.72 vs. 0.97 hours; 95% CI, 0.46-3.05) and a significantly greater reduction in off time (2.75 vs. 0.96 hours; 95% CI, 3.03 to 0.54), according to results.

Researchers reported adverse events in 63 of 74 patients in the foslevodopa-foscarbidopa group and 42 of 67 in the levodopa-carbidopa group; serious adverse events were similar between the groups (6 of 74 vs. 4 of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site-related and included erythema, pain, cellulitis and edema, most of which were nonserious and mild to moderate in severity.

Sixteen of 74 participants in the foslevodopa-foscarbidopa group discontinued the study drug because of adverse events, compared with one of 67 participants in the oral levodopa-carbidopa group.

“As a 24-hour per day [continuous subcutaneous infusion], foslevodopa-foscarbidopa delivers a wide range of therapeutically relevant doses that can control motor symptoms and reduce motor fluctuations in patients with advanced Parkinson’s disease and offers a potentially safe and effective, individualized and nonsurgical alternative to available treatments,” Soileau and colleagues wrote.