Objective: To provide guidance on dosing of IPX203 based on clinical trial experience.

Background: IPX203 is an extended-release, oral carbidopa-levodopa (CD-LD) formulation designed to rapidly attain therapeutic plasma LD concentrations and maintain them for 6-7 hours. The formulation results in approximately 85% bioavailability of levodopa in terms of total exposure (AUC) and 38% maximum plasma LD concentrations (C_max) compared to an equivalent dose of immediate-release (IR) CD-LD. Because of these differences, it is critically important to recognize that dosages of IPX203 are not interchangeable with IR CD-LD.

Method: RISE-PD was a randomized, double-blind, active-controlled, Phase 3 study of the safety and efficacy of IPX203 vs IR CD-LD in Parkinson’s disease patients with motor fluctuations. All patients underwent a 3-week open-label IR CD-LD dose adjustment, a 4-week open-label conversion to IPX203, followed by randomization to a 13-week double-blind treatment with IR CD-LD or IPX203. Suggested initial dosing conversion to IPX203 was based on the prior most frequent individual IR LD dose. The conversion ratio for IPX203 from IR CD-LD was 2.8, and IPX203 was administered approximately every 6-8 hours for most patients.

Results: Overall, following conversion and optimization, patients with motor fluctuations required about 1.79 times the mean daily LD mg dose compared to IR CD-LD, and on average, individual doses were 2.9 times the mean most frequent stable individual dose of IR CD-LD. The higher daily dose was needed to avoid the troughs in plasma LD concentrations seen with IR CD-LD and the higher single dose was needed to obtain peak plasma concentrations close to those obtained from IR CD-LD.

Conclusion: When converting patients from IR CD-LD to IPX203, it is important to try to match the C_max of IR CD-LD to provide the same level of expected benefit for the patient. Patients experiencing motor fluctuations on IR CD-LD can be converted to IPX203 by multiplying the most frequent individual dose of IR CD-LD by 2.8 and administering it on average 2 to 4 times daily, followed by titration according to clinical response. It is critical to inform patients that the initial regimen is just a starting dosage and subsequent adjustments based on clinical response are likely.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/how-to-dose-extended-release-carbidopa-levodopa-capsules-ipx203-in-parkinsons-disease-patients-experience-from-the-phase-3-clinical-trial/