Extended-Release Carbidopa/Levodopa Shows Tolerable Safety, Maintained Efficacy in Open-Label Extension
The majority of treatment-emergent adverse events from IPX203 were mild or moderate in nature, and occurred within the first 90 days of treatment.
Alberto J. Espay, MD, MSc
IPX203 (Amneal Pharmaceuticals), an investigational extended-release carbidopa/levodopa (CD-LD) agent, demonstrated a favorable safety and tolerability profile seen up to 9 months, with efficacy measures that were maintained from baseline to end of the study. The therapy is currently under review by the FDA as a potential treatment for Parkinson disease (PD), with a scheduled PDUFA date of June 30, 2023.
These findings, presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, were from an open-label extension trial comprised of patients who completed the phase 3 double-blind, RISE-PD study (NCT03670953). RISE-PD consisted of a 3-week open-label dose adjustment phase, followed by a 4-week open-label conversion to IPX203, and a 13-week double-blind maintenance phase. In total, 419 patients with PD were enrolled and received treatment, with 384 (84%) completing the study.
Led by Alberto J. Espay, MD, MSc, director, James J. and Joan A. Gardner Family Center, and research chair, Parkinson’s Disease and Movement Disorders, University of Cincinnati Health, all efficacy measures were stable throughout the study period of 9 months. Among the 67 (16%) patients who discontinued treatment, the reasons included withdrawal (n = 22; 32.8%), adverse events (AEs)(n = 20; 29.9%), and lack of efficacy (n = 14; 20.9%).
Most treatment-emergent AEs were either mild or moderate in severity, and occurred within the first 90 days of treatment. Of them, the most common were dyskinesia (n = 21; 5.0%), fall (n = 21; 5.0%), urinary tract infection (n = 21; 5.0%), back pain (n = 15; 3.6%), constipation (n = 11; 2.6%), and COVID-19 (n = 10; 2.4%). The average daily dosing frequency of IPX203, 3.1 (standard deviation [SD], 0.45) times/day, was generally stable over the 9-month period, with most patients reaching a stable dosing regimen by 3 months of treatment. Additionally, the mean daily dose of IPX203 was 1539.61 (±630.83) and the median treatment duration was 271 (range, 16-369) days.
In the original RISE-PD study, published in Neurology in early 2022, IPX203 met its primary end point, demonstrating statistically significant improvement in good ON time relative to CD/LD immediate release capsules (0.53 hr; P = .0194). On secondary end points, treatment with the therapy resulted in significantly less OFF time compared with CD/LD immediate release (–0.48 hr; P = .0252). For Patient Global Impression of Change scores, 29.7% of IPX203-treated patients were “much improve” or “very much improved” compared with 18.8% of those on CD/LD immediate release. Both groups demonstrated similar scores on Movement Disorder Society-Unified Parkinson’s Disease Rating scale.
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