Bioequivalence and Bioavailability Forum

Dear beman,
to demonstrate bioequivalence you need to show that the 90% CI are within the acceptance range in both states, under fasting as well as under fed conditions. Do you really need to know the size of the food effect? IMHO not since the food effect of the originator formulation is known and as long as your formulation is bioequivalent in both conditions it is more or less the same with your formulation. Therefore I would keep the design as simple as possible. The current EMA-Guideline states, that it is acceptable to conduct either two seperate 2x2-crossover studies or a four way crosssover study. Using the four way crossover study design would give you the possibility to determine the size of the food effect but you will have a higher risk of drop outs, you can not adapt sample sizes in case the two conditions differ in their variability, you can not conduct the evaluation in sequence which reduces the risk of additional costs in case of failure etc.....
Therefore I prefer two 2x2 crossover studies.
I hope this helps
Kind regards
Dr_Dan