Bioequivalence and Bioavailability Forum

Hi Mittyri,

❝ Suppose the Sponsor uses the sequences (S1: C -> D -> A -> B; S2: D -> C -> B -> A) and the Fed part fails to show BE while the fasted part passes.

❝ If the sponsor decides to reformulate, my understanding is that this would require starting over, since a new formulation would invalidate both the fed and fasted data. Is that correct?

Yes, it is.

❝ Alternatively, if the Sponsor believes the fed miss was a play of chance in a study powered at 80%, he can run another fed study with a larger sample while retaining the original fasted results for submission.

Makes sense to me.

❝ How are reviewers likely to view the initial fed failure alongside a clean fasted outcome?

If the fed part was underpowered, I don’t see a problem.

❝ Would submitting both studies make the package look problematic, or is this generally acceptable provided the second fed study succeeds?

I don’t think so. You have to submit the synopsis of the fed part anyway. If an assessor wants to dig deeper, you have to submit the complete report. However, the second – properly powered – study overrules the fed part of the first.