A Phase 3 Trial of IPX203 vs CD-LD IR in Parkinson’s Disease Patients with Motor Fluctuations (RISE-PD)
Robert A. Hauser1, Alberto J. Espay2, Peter LeWitt3, Aaron Ellenbogen4, Stuart Isaacson5, Rajesh Pahwa6, Fabrizio Stocchi7, Hester Visser8, Richard D'Souza8
1Movement Disorders Center, 2University of Cincinnati, 3Henry Ford Hospital - Franklin Pointe, 4QUEST Research Institute, 5Parkinson's Disease & Movement Disorders Center of Boca Raton, 6University of Kansas Medical Center, 7IRCCS San Raffaele Pisana, 8Amneal Pharmaceuticals
Objective:

To evaluate the safety and efficacy of IPX203 vs carbidopa-levodopa (CD-LD) immediate-release (IR) in Parkinson’s disease (PD) patients experiencing motor fluctuations.

Background:

IPX203 is an investigational oral extended-release (ER) formulation of CD-LD, designed to provide rapid absorption of LD to quickly reach a desired plasma concentration, and to maintain LD concentrations within the therapeutic range for a longer duration than CD-LD IR, with less peak-to-trough fluctuation.

Design/Methods:

Randomized, double-blind, active-controlled study consisting of 3-week open-label CD-LD IR dose adjustment; followed by a 4-week open-label conversion to IPX203; and a 13-week double-blind maintenance phase. The trial was conducted at 108 clinical sites in the U.S. and Europe. 506 subjects with PD age 40 years or older were randomized; 449 finished the study. Subjects were required to have an average of at least 2.5 hours daily “Off” time during waking hours. Efficacy was measured at week 20, defined as change from the baseline. 

Results:

The study met its primary endpoint, demonstrating statistically significant improvement in “Good On” time for IPX203 compared to CD-LD IR (0.53 hr, p=0.0194).

The secondary endpoint of change from baseline in “Off” time showed IPX203 treatment resulted in significantly less “Off” time compared with CD-LD IR (-0.48 hr, p=0.0252). Analysis of secondary endpoint for Patient Global Impression of Change scores (PGI-C) showed 29.7% of patients treated with IPX203 were “much improved” or “very much improved” compared with 18.8% of CD-LD IR-treated patients (p=0.0015). MDS-UPDRS Part III change from baseline scores were similar for both treatment groups.

Most common TEAEs were nausea, falls and UTI.

Conclusions:

In the RISE-PD study, IPX203 showed statistically significant improvement in “Good On” time compared to CD-LD IR, when dosed on average 3 times a day compared to 5 times a day for CD-LD IR.