Bioequivalence and Bioavailability Forum

Dear all

We found in one of the study subjects, drug levels above LLOQ at the pre-dose sample of the first study period.
This came out on both analytes under study (ethinyl estradiol and gestodene), somehow confirming this was not an artifact.

Since levels were below 5% of the Cmax, our first approach was to include this subject in the analysis anyway.
It was also noticed that the statistical analysis shows a significant sequence effect (p ~= 0,048)

Sequence effect does not show up taking this subject out of the analysis. I think this is just a coincidence since the pk profile for this subject is almost coincident for both ref and test drugs. (Cmax 325.46 vs 315.95 pg/mL and AUC 0-t 2859 vs 3017 [pg x hr]/mL, for ethinyl, for example).

I'm wondering what would be the "best" approach to report the final results - including or excluding this volunteer - since our regulators usually "don't like" volunteer exclusions.
By the way, BE results are the same (bioequivalent) including or excluding this volunteer from the BE analysis.

Thanks in advance for your comments

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Edit: Category changed. [Helmut]