Bioequivalence and Bioavailability Forum

Hi all,

Would appreciate all your comments with the following scenario... I recently ran a FDA BE study involving an IR product with a long and variable t1/2. The literature value is around 25 hrs with an upper range of 60 hr. I ran a small pilot study (n=6) and the results showed that 96 hours sampling was more than adequate to capture 90% of the PK profile (Helmut will scream at me for using n=6 ).

My pivotal study finished with 44 subjects. The study population showed a mean t1/2 of 25 hrs (Range 12-67 hrs) for each treatment. I went ahead with PK blood sampling for 96 hrs (timept before 96 hr was 72 hr). Based on 96 hour sampling, the mean(AUCt/AUCinf) ratio was about 92% for each treatment. Individual data showed 3 subjects to have AUCt/AUCinf ratio of 60% with a t1/2 of greater than 60 hours.

Maybe this is a silly question... Do you think that I might get question from the agency about the 3 subjects? Since the mean t1/2 from each treatment arm was 25 hrs with an upper range of 67 hrs, I can re-evaluate the data as a truncated design (if being asked) and compute AUC0-72.

The result as is for both AUC and AUCi are dead since the 90% CIs were well within 80-125% (Ratio~100%, intra CV~10%). Washout was adequate(3 wks) with no carryovers. I don't have an issue with computing AUC0-72(pass anyway) but I was just curious if I would even get a question from FDA regarding the 3 subjects.

Thanks
John