Abstract Details

Title CREXONT® (IPX203, ER CD-LD) Super-responders: Enhanced Symptom Control in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 17-003

Objective To assess if CREXONT^® (IPX203) improves absorption by evaluating whether patients with poor IR CD-LD response show greater clinical improvement after switching to CREXONT.

Background CREXONT is the first extended-release (ER) CD-LD formulation designed to optimize absorption in the proximal small intestine. The new formulation intended primarily to extend dose duration, could also mitigate levodopa absorption challenges in some Parkinson’s disease patients. Such patients may be initiated on doses too high by the current conversion algorithm, increasing risk of dopaminergic adverse events. This analysis describes the range of responses to formulation change observed in the RISE-PD trial and highlights those requiring dose reductions when converting to CREXONT.

Design/Methods During the open-label conversion phase of RISE-PD, all participants were converted from IR CD-LD to CREXONT using a predefined conversion algorithm. We modeled the effects of formulation change on dose-response (δ), defined as a patient’s daily “Good On” time(h) per their total daily levodopa dose (TDD-LD). Gaussian Mixture Models (GMMs) were used to isolate putative populations based on δ values.

Results After conversion to CREXONT, GMMs isolated two main response types: A main population ([MP], 93% of subjects) of lower δ values (n=470, mean=0.88h), and a smaller population (7%) of “super-responders” (SR) whose d values indicated increased dose-response benefits associated with conversion (n=35, mean=5.08h). Compared to MP, while on IR CD-LD, SR were on higher TDD (1003mg [SR] vs 855mg [MP], p=0.05) and had lower dose-responses (0.99h/100mg [SR] vs 1.45h/100mg [MP], p=0.0007). On average, after using the predefined IR CD-LD to CREXONT conversion algorithm, SR needed reductions from their CREXONT starting dose (-213mg of TDD), while MP needed an increase (+144mg of TDD, p=1.1x10^-6).

Conclusions Patients with short response durations on high doses of IR CD-LD are most likely to have enhanced response to CREXONT and may require lower doses than suggested by the dosing algorithm.

Authors/Disclosures
Simon Allard, PhD (Amneal Pharmaceuticals) PRESENTER	Dr. Allard has received personal compensation for serving as an employee of Amneal.
Ghazal Banisadr, PhD (Amneal Pharmaceuticals)	Dr. Banisadr has received personal compensation for serving as an employee of Amneal Pharmaceuticals.
Stanley Fisher, MD, FAAN	Dr. Fisher has received personal compensation for serving as an employee of Amneal Pharmaceuticals.
Peter A. LeWitt, MD (Henry Ford Hospital - Franklin Pointe)	Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ONO Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. The institution of Dr. LeWitt has received research support from Michael J Fox Foundation.

��ɫ��

��ɫ��