Objective: To generate quantitative data helping dose optimization when converting Parkinson’s disease (PD) patients from IR CD-LD to IPX203.

Background: IPX203 is the first extended-release (ER) CD-LD formulation that includes a mucoadhesive polymer designed to optimize absorption in the proximal small intestine. While the primary intent was to increase dose duration, this formulation feature could also compensate for absorption issues affecting a subset of PD patients. In this scenario, patients experiencing absorption issues addressed by IPX203’s formulation would be initiated at doses too high by the current conversion algorithm, making them more likely to experience dopaminergic adverse events like dyskinesia. While this analysis cannot determine if IPX203 corrects absorption issues, it carefully describes the range of responses to formulation change observed in the RISE-PD trial. We provide data describing patients needing dose reductions when converting to IPX203.

Method: During the open-label conversion phase of the RISE-PD trial, all participants were converted from IR CD-LD to IPX203 using a predefined conversion algorithm. We modeled the effects of formulation change on dose-response, defined here as a patient’s daily “Good On” time (h) per their total daily LD dose (TDD-LD). Gaussian Mixture Models (GMMs) were used to isolate putative populations based on dose-response values.

Results: After conversion to IPX203, GMMs isolated two main response types: A main population ([MP], 93% of subjects) of lower dose-response values (n=470, mean=0.88h), and a smaller population (7%) of “super-responders” (SR) whose dose-response 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 IPX203 conversion algorithm, SR needed reductions from their starting dose of IPX203 (-213mg of TDD), while MP needed an increase (+144mg of TDD, p=1.1×10^-6).

Conclusion: When patients with lower dose-responses to IR CD-LD are converted to IPX203, it is likely that a dose reduction is needed within 1-3 days after they start IPX203.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ipx203-er-cd-ld-super-responders-description-of-a-patient-subpopulation-reaping-extra-benefits-in-dose-response-when-converting-from-ir-cd-ld/