FDA CRL - Impax Laboratories, LLC.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Impax Laboratories, LLC, for their New Drug Application (NDA 217186) for Crexont (carbidopa and levodopa) Extended Release Capsules. Submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, the application cannot be approved in its current form.

Key issues include an inadequate scientific bridge for carbidopa pharmacokinetic exposure. Studies revealed significantly higher carbidopa exposure from Crexont compared to reference products Sinemet or Rytary, preventing reliance on their established safety profiles. Consequently, the long-term safety database for Crexont was deemed insufficient. The FDA required a minimum of 100 patients treated for one year, with a substantial portion at the highest intended dose (based on modal dose), but the submission only included 67 patients with 12-month exposure, and none at the highest dose.

Required actions for Impax include submitting long-term safety data for 100 patients with 12-month continuous exposure, with a significant proportion at the highest modal dose. Alternatively, the company could reformulate Crexont to align carbidopa exposure with a listed drug, followed by a relative bioavailability study. Additionally, a thorough QT study is mandated to assess Crexont's potential cardiac effects. Impax must also provide a comprehensive safety update as per regulatory guidelines and respond to the deficiencies within one year.