Bioequivalence and Bioavailability Forum

Dear Mathews,

❝ do u have any idea about the intra CV of Lansoprazole?

Regrettably, yes...

❝ I want to find the Sample Size for a single dose 2 x 2 crossover design under fasting condition.

❝ So which CVintra is best for finding the Sample Size?.

❝ If we use the CVintra for Cmax value, the number of subjects required is almost double than that of CVintra of AUC value?

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That’s a pitty, but you have to demonstrate BE for both AUC and C_max, although you may widen the acceptance range for C_max to 0.75–1.33 based on clinical grounds and the high variability. If the study is intended for submission in the EU, some countries will accept literature data showing high variability (e.g., UK), whereas others (e.g., NL), will ask for a replicate design study to show that the reference is a HVDP (see the Q&A document):

A high CV as estimated from the ANOVA model is thus an indicator for high within-subject variability. However, a replicate design is needed to assess within-subject variability.

There have been already a couple of threads concerning *prazoles and problems with high variability, gastric resistance, and outliers.

I’ve seen studies succeeding with sample sizes of 32, and others failing in 90+…