Duration of Benefit Per Dose: Post Hoc Analysis of ”Good On” Time Per Dose for IPX203 vs CD-LD IR in the RISE-PD Phase 3 Trial
Robert A. Hauser1, Hubert H. Fernandez2, Kevin Klos3, Susan Criswell4, Neepa Patel5, Ghazal Banisadr6, Stanley Fisher6
1Movement Disorders Center, 2Center for Neurological Restoration, Cleveland Clinic, 3The Movement Disorder Clinic of Oklahoma, 4Washington University, 5Rush University Medical Center, 6Amneal Pharmaceuticals
Objective:

To determine the mean duration of “Good On” time per dose for IPX203 in comparison to carbidopa-levodopa (CD-LD) immediate-release (IR) in Parkinson’s disease (PD) patients with motor fluctuations.

Background:

Approximately 50% of PD patients develop motor fluctuations within 5 years of treatment with levodopa. Convenient, highly effective, and well tolerated therapies that maintain therapeutic levodopa levels throughout the day are needed. IPX203 is a long-acting, oral CD-LD formulation. It was evaluated vs CD-LD IR in PD patients with motor fluctuations in a phase 3, double-blind, randomized study. A key metric to characterize the potential benefit of a long-acting levodopa formulation is duration of “Good On” time per dose.

Design/Methods:

We performed a post hoc analysis of the RISE-PD study. Least squares (LS) mean “Good On” time per dose was calculated at the end-of-study (EOS) visit for the modified intention-to-treat (mITT) population for IPX203 and CD-LD IR treatment groups using an MRMM model. “Good On” time per dose was defined as daily “Good On” time (hours) divided by daily dosing frequency in the subject's stable dosing regimen.

Results:

At the end of the double-blind treatment period, the mITT population consisted of 495 subjects, who had a mean age of 66.3yrs (8.91), and mean age of PD onset of 58.1yrs (9.34), of whom 65.9% were men. At baseline, the CD-LD IR (n=246) and IPX203 (n=249) groups had a mean daily “Off” time of 3.96 (2.52) hours and 4.02 (2.47) hours respectively. At EOS visit, CD-LD IR and IPX203 provided 2.21 hours and 3.76 hours of “Good On” time per dose respectively (p<0.0001).

Conclusions:

IPX203 provided 1.55 more hours of “Good On” time per dose vs CD-LD IR, representing a 70% increase. Information from this post hoc analysis may help clinicians make better medication management decisions and anticipate the results of conversion from CD-LD IR to IPX203.