Bioequivalence and Bioavailability Forum

Dear Yuvraj,

just some desultory thoughts.

❝ Recently, I have analysed one Pilot study data.

❝ T/R ratios for Cmax, AUC0-t and AUC0-inf were 99.64%, 96.14% and 116.66%.

I’m surprised by the large discrepancy in PEs between AUC_t and AUC_inf. It looks like the test has a longer apparent elimination than the reference. For immediate release products this should not be the case (actually we assume constant clearances). If you had modified release formulations, you may be trapped by flip-flop-pharmacokinetics (the slowest phase is absorption). In such a case AUC_t as the primary target parameter is not trustworthy (remember: in BE we are interested in equivalence of absorption). Therefore we must concentrate on AUC_inf. What’s the percentage of extrapolated AUC (mean, min, max) by formulations? If you really have to deal with a flip-flop, you must sample long enough (e.g., residual area 5% instead of 20%).

❝ 90% CI were not within the Bioequivalence Limit (80%-125%).

Doesn't matter. That's not the target of a pilot.

❝ Now, I want to calculate sample size for Pivotal Study,

❝ Is it right way to calculate sample size based on assumption (i.e maximum 10% T/R ratio difference?

No, don’t do that! Give us more information. First we have to find an explanation for the discrepancy between AUC_t and AUC_inf. I have my doubts whether it will be possible to demonstrate BE for AUC_inf in a reasonable sample size (80% power, PE 116.66%):
  CV%  n
  15   60
  20  104
  25  160
  30  226