Patients on IPX203 received less doses than those on traditional immediate-release carbidopa/levodopa and demonstrated 0.53 more hours of good ON time per day than IR CD/LD.
Months after the FDA issued Amneal Pharmaceuticals a complete response letter (CRL) for its investigational Parkinson disease (PD) agent IPX203, investigators have published the full dataset of RISE-PD, the phase 3, double-blind study (NCT03670953) used to support the agent’s application. All told, patients treated with the extended-release carbidopa-levodopa (CD/LD) solution showed more hours of good ON time per day than those on immediate-release (IR) CD/LD.
Published in JAMA Neurology, the study consisted of a screening period lasting up to 4 weeks, a 3-week open-label IR CD/LD dose-adjustment period, a 4-week open-label IPX203 dose-conversion period, and a 13-week double-blind, double-dummy treatment period. All told, the trial met its primary end point, as those dose with IPX203 (n = 256) 3 times per day showed a statistically significant improvement of 0.53 hours (95% CI, 0.09-0.97; P = .02) in daily good ON time relative to those on IR CD/LD (n = 250), who were dosed 5 times per day.
Data from RISE-PD supported IPX203’s new drug application, which was accepted by the FDA in November 2022. When the FDA handed Amneal the CRL for IPX203 in July 2023, it stated that the decision was not based on efficacy or manufacturing for the agent, but rather the established safety for an ingredient of the therapy. The agency noted that the pharmacokinetic data for the safety of levodopa was sufficient, but it needed additional data for the second ingredient, carbidopa.
Led by Robert A. Hauser, MD, director of the Parkinson’s and Movement Disorders Center at the University of South Florida, 449 patients (88.7%) completed the study. The secondary end point of change from baseline in OFF-time in hours per day showed that IPX203 treatment resulted in significantly less OFF-time compared with IR CD/LD (difference in least square [LS] means, –0.48; 95% CI, –0.90 to –0.06; P = .03). Between the groups, 29.7% and 18.8% of patients on IPX203 and IR CD/LD, respectively, rated themselves as much improved or very much improved on PGI-C (P = .002).
For patients on IPX203, treatment-emergent adverse events (TEAEs) were most frequent in the double-blind period (42.2%) than the dose-conversion (38.9%) or dose-adjustment (18.7%) periods. Within this group, 34 discontinued treatment from the double-blind period, 14 from AEs, 10 withdrew, 5 because of lack of efficacy, 3 with protocol deviations, 1 noncompliant, and 1 for other reasons. During the double-blind period, 16.4% of 6.8% of patients on IPX203 and IR CD/LD, respectively, experienced treatment-related TEAEs. Eight patients treated with IPX203 (3.1%) and 4 treated with IR CD/LD (1.6%) experienced serious TEAEs.
Among those treated with IPX203, the most frequently reported TEAEs were nausea (4.3%), anxiety (2.7%), and dizziness (2.3%), while those on IR CD/LD mostly experienced fall (3.6%), urinary tract infection (3.2%), and back pain (2.8%). No clinically relevant treatment group differences were noted for laboratory parameters, vital signs, and electrocardiogram results. There were no deaths reported as well.
By the end of the study, data showed that patients on IPX203 experienced a longer duration of good ON time per dose (LS mean, 3.76 hours; 95% CI, 3.62-3.91) vs those on IR CD/LD (LS mean, 2.21 hours; 95% CI, 2.07-2.36). When compared with IR CD/LD, treatment with IPX203 resulted in a mean increase in good ON time per dose of 1.55 hours (difference in LS means, 1.55; 95% CI, 1.37-1.73; P <.001). Although mean dosing frequency was less frequent on IPX203 (3.04 vs 5.01 hours), a pill burden analysis showed a slightly higher number of daily pills for IPX203 (10.6 [SD, 4.2]) than IR CD/LD (8.7 [SD, 3.8]).