Extended-release carbidopa-levodopa scores over immediate release carbidopa-levodopa in Parkinson's disease: JAMA

A recent clinical trial has demonstrated the superior efficacy of IPX203, an extended-release formulation of carbidopa-levodopa, over the conventional immediate-release carbidopa-levodopa for parkinsonism. The RISE-PD study aimed to evaluate the effectiveness and safety of IPX203 in patients experiencing motor fluctuations, a common challenge in managing Parkinson's disease.

Parkinson's disease, a neurodegenerative disorder, often leads to motor symptoms like tremors, stiffness, and bradykinesia. Managing these symptoms efficiently is crucial for the quality of life of patients. However, one of the limitations in the treatment arsenal has been the short half-life and absorption window of levodopa, the primary medication for managing these symptoms. IPX203 was designed to address this limitation by offering an extended-release formulation of carbidopa-levodopa.

The RISE-PD trial, conducted between November 2018 and June 2021 across 105 clinical centers in the US and Europe, enrolled 630 patients with Parkinson's disease. These patients, who were experiencing an average of 2.5 hours or more daily off-time despite their medication, were included in the study. After a dose adjustment period, they were randomized to receive either IPX203 or immediate-release carbidopa-levodopa for 13 weeks.

The primary endpoint of the trial was the mean change in daily good on-time (time without troublesome dyskinesia) from baseline to the end of the double-blind treatment period. The results were nothing short of remarkable. IPX203 demonstrated a statistically significant improvement in daily good on-time compared to the immediate-release carbidopa-levodopa, with patients on IPX203 experiencing an increase in good on-time by 1.55 hours per dose. Importantly, IPX203 was dosed fewer times per day, offering greater convenience to patients.

Safety considerations were equally important, and IPX203 showed a favorable safety profile in the trial. Nausea and anxiety were reported as the most common adverse events, with a slightly higher incidence in the IPX203 group.

This breakthrough in Parkinson's disease management holds significant promise for patients worldwide. IPX203 not only improved the quality of good on-time for patients but also reduced the dosing frequency, which could enhance patient compliance and convenience. The study's findings signify a crucial step forward in addressing the unmet needs of Parkinson's disease patients experiencing motor fluctuations.

Reference:

Hauser, R. A., Espay, A. J., Ellenbogen, A. L., Fernandez, H. H., Isaacson, S. H., LeWitt, P. A., Ondo, W. G., Pahwa, R., Schwarz, J., Fisher, S., Visser, H., & D’Souza, R. (2023). IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease. In JAMA Neurology. American Medical Association (AMA). https://doi.org/10.1001/jamaneurol.2023.2679