Objective:

To provide clinical evidence of improved efficacy (“Good On” time) with optimizing immediate-release carbidopa-levodopa (IR CD-LD) or an extended-release CD-LD (IPX203) treatment.

Background:

IPX203 is an extended-release (ER), oral CD-LD formulation designed to rapidly attain therapeutic plasma LD concentrations and maintain them for 6-7 hours. IPX203 was studied in a phase 3 study (RISE-PD) that included a double-blind phase and a 9-month open-label extension.

Design/Methods:

RISE-PD was a randomized, double-blind, active-controlled phase 3 study of the safety and efficacy of IPX203 vs IR CD-LD in PD patients with motor fluctuations. All patients underwent a 3-week open-label IR CD-LD dose adjustment and a 4-week open-label conversion/optimization to IPX203, followed by randomization to a 13-week double-blind treatment with IR CD-LD or IPX203. Data from the IR CD-LD dose optimization and IPX203 dose conversion/optimization phases are important to understand potential improvement in efficacy with optimizing dosing regardless of whether the patient is on IR or ER CD-LD.

Results:

Patients entering the study had a daily “Good On” time of 9.5 hours. “Good On” time was improved to 10.3 hours at the end of the IR CD-LD dose adjustment phase and to 11.7 hours at the end of the IPX203 dose conversion/optimization phase. Patients needed on average (mean +/- SD) of 0.9 +/- 1.2 steps and 5.7 +/- 6.0 days to optimize their IR CD-LD dose. Stable dosing in the IPX203 conversion period was achieved in 1.6 +/- 1.74 titration steps and 17.2 +/- 3.7 days. A total of 630 patients entered the IR dose optimization phase and 589 entered the IPX203 dose conversion/optimization phase.

Conclusions:

Patients experiencing motor fluctuations when taking oral CD-LD can experience improvement with dose optimization of IR CD-LD and further benefit with conversion to and optimization of IPX203.