Novel Formulation of Carbidopa/Levodopa Under Review for Parkinson Disease

The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for IPX203 for the treatment of Parkinson disease (PD). 

IPX203 is a novel, oral formulation of carbidopa/levodopa extended-release capsules, which contain immediate-release (IR) granules and extended-release (ER) beads. The IR granules consist of carbidopa and levodopa with a disintegrant polymer to allow for rapid dissolution. The ER beads consist of levodopa coated with a sustained release polymer to allow for slow release of the drug.

The NDA is supported by data from the multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group phase 3 RISE-PD trial (ClinicalTrials.gov Identifier: NCT03670953), which compared the efficacy and safety of IPX203 to carbidopa/levodopa (CD/LD) IR for the treatment of patients with PD who have motor fluctuations.

The trial included a 3-week, open-label CD/LD IR dose adjustment period and a 4-week, open-label period for conversions to IPX203, followed by a 13-week double-blind treatment period in which patients were randomly assigned 1:1 to receive either IPX203 (with matching placebo) or CD/LD IR (with matching placebo). 

At week 20, results showed that treatment with IPX203 met the primary endpoint demonstrating a statistically significant improvement in “Good On” time of 0.53 hour when dosed on average 3 times a day compared with CD/LD IR when dosed on average 5 times a day (P =.0194).

Treatment with IPX203 was also associated with significantly less “Off” time (secondary endpoint) compared with CD/LD IR (-0.48 hour; P =.0252). Moreover, an analysis of Patient Global Impression of Change scores showed that 29.7% of IPX203-treated patients reported being “much improved” or “very much improved” compared with 18.8% of patients treated with CD/LD IR (P =.0015). Nausea was observed to be the most common adverse reaction.

A Prescription Drug User Fee Act (PDUFA) target date of June 30, 2023 has been set for the application.

References

1. Amneal announces US FDA filing acceptance of New Drug Application for IPX203 for the treatment of Parkinson’s disease. News release. Amneal Pharmaceuticals, Inc. Accessed November 11, 2022. https://www.businesswire.com/news/home/20221109005842/en/Amneal-Announces-U.S.-FDA-Filing-Acceptance-of-New-Drug-Application-for-IPX203-for-the-Treatment-of-Parkinson%E2%80%99s-Disease
2. Hauser RA, Espay AJ, LeWitt P, et al. A phase 3 trial of IPX203 vs CD-LD IR in Parkinson’s disease patients with motor fluctuations (RISE-PD) (S16.010). Published online May 3, 2022. Neurology.