Bioequivalence and Bioavailability Forum

Hi Helmut,

Thanks very much for your prompt reply!

❝ Oops, that's a wrong design! PK interaction studies must be performed as a cross-over. Imagine a situation, where you have a 'true' period effect. In a cross-over study the treatment effect will not affected. In the paired design you suggested it is not possible to separate any period effect from the treatment effect!

You are right about the period effect. In the design I mentioned, it is impossible to separate the period effect from the effect. But the following FDA guidance says:
"A study can use a randomized crossover (e.g., S followed by S+I, S+I followed by S), a one-sequence crossover (e.g., S always followed by S+I or the reverse), or a parallel design (S in one group of subjects and S+I in another)."

http://www.fda.gov/cder/guidance/2635fnl.pdf
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf

Is this true?

❝ BTW, don't forget that PK interaction studies are to be perfomed in steady state (FDA: recommended, EMEA: mandatory).

Sorry, I forgot to mention that Drug B will be dosed for several days right before the A+B dose in period 2.


Thanks,
xz

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Edit: Link corrected for FDA's new site. [Helmut]