Bioequivalence and Bioavailability Forum

Hi Alex,

❝ Hello to all! first thanks for this wonderful forum, here a young MD, clinical pharmacologist recently moving from clinical trials conduct to design, tryinto apply my (modest) knowledge of clinical PK and biostatistics to phase I trial design.

Welcome to the club!

❝ I was discussing with a former colleague. If we were to design a trial to try to support a change in SmPC for a certain product, ie. a faster absorption:

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❝ - If we were to demostrate in overall a faster absorption, we would need to design a superiority trial and calculate N based on expected diff in logCmax using logsd (difference or more conservative the higer Cmax maybe?). Suggested log to use a diff in means to calculate N and Cmax as is the parameter to include both extentand and rate of absorption (I deem Tmax as useless).

Since both formulations are IR, only the rate of absorption changes. The extent of absorption should not be affected (unless you have pre-systemic metabolism and run into saturation with the ‘faster’ formulation).

❝ -If we were to demonstrate a faster absorption at X point (10 minutes), before Tmax, shall I need to use the differences in logAUC with same SD assessment?

In principle, yes.

❝ or concentration at 10 minutes would suffice (or maybe any approach is not correct at all).

Not sure, what you mean. If you want to avoid a clinical trial and bridge to the safety/efficacy data of the ‘old’ formulation, consider bracketing. That means, non-superiority for C_max and equivalence for AUC.

❝ I assume I would calculate N based on the difference in means as in any study.

Yes.

❝ PS. I swear I conducted an intensive research through the forum

Although that’s rare, I believe it.