Impax Laboratories, LLC: Crexont Extended Release

IPX203-B16-05, and IPX203-B14-02, an adequate scientific bridge was not established for the carbidopa pharmacokinetic (PK) exposure between IPX203 and Sinemet or Rytary at the highest proposed dosage regimen of Crexont, although an adequate scientific bridge was established for the safety of levodopa based on PK exposure.

FDA's finding of safety for Sinemet or cross-reference Rytary for the safety of carbidopa for the approval of Crexont.

Clinical trials must be adequate to support the safety of chronic exposure to the higher levels of carbidopa that patients would receive with Crexont compared with these two listed drugs.

Furthermore, the long-term safety database is insufficient to adequately characterize the long-term safety of Crexont for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Alternatively, you may consider reformulating your proposed product to reduce exposure of carbidopa to levels that are comparable to a listed drug and can be supported by a relative bioavailability study.