Bioequivalence and Bioavailability Forum

Dear ioanam!

❝ I have to perform a 3 way cross over pilot study.

❝ The test product is available in 4 strengths (e.q. 250, 500, 750 and 1000 mg) with dose proportionality between these strengths. The pharmacokinetics is not influenced by food.

❝ Is a good design for this study a 3 way crossover study in fasted conditions with 3 sequences, 3 treatments and 3 periods with:

❝ Test A – test product 4 x 250 mg

❝ Test B – test product 1000 mg

❝ Reference – reference (1000 mg)?

Yes, that’s a reasonable design, with the exeption that you should apply a six sequence design. For details see this post.

If in a later stage you go for a pivotal study you should consult the regulatory agency, since e.g., some European regulators want to see for such a design (2 test formulations) a Bonferroni-corrected confidence interval (95% instead of 90%) in order to keep the patient’s risk at 5% (EMEA’s Points to Consider on Multiplicity Issues in Clinical Trials).