Bioequivalence and Bioavailability Forum

Dear Helmut,

I have results from a pilot study with 2 test products (T1 and T2) against R, administered in 3 periods, two analytes. 17 subjects out of 18 completed the study.

I'd like to have some guidance for the BE analysis for WinNonlin 6.3. What would be the best approach? Could you please kindly guide?

I included T1 and T2 in one NCA and run the bioquivalence as one dataset for each analyte. To run the NCA I included columns to distinguish formulations (my columns are: analyte, subject, period, formulation, sequence, time, concetration). Do I need to calculate intrasubject variability as described below or it's just written in the final variance parameters as var(residual) (which seems to be little bit low)?

I can separate T1 and T2 and run them against the R separetely also but would it make a difference?

If I need to calculate CVintra manually, I couldn't figure out the step below. Do I hit OK after Column [Parameter] and then another step to exclude?

Thank you very much in advance for your answer.

Regards,
BRN

❝ – Options > Filter > Add > ● Built In > Add… > Action [Include] > Find [Var(Residual)] > Column [Parameter] > Exclude ● Units, Parameter > OK

❝ – Options > Transformation > Add > Transformation Type [Custom] > New Column Name [CVintra] > Formula [100*sqrt(exp(Estimate)-1)]

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I figured out how to calculate the CVintra, so nevermind the related question.

However, still can't figure out what's the best approach for presenting results.

I used A, B and C letters for T1, T2 and Reference products respectively not to enter T1T2R in the sequence column. Then I did 2 types of analysis.

1-Run the analysis on the complete data set. Getting these results (PE, 90%CI U - L):

A, Cmax, 103.92 (83.42-129.46), CVintra: 39.1%
B, Cmax, 96.01 (77.07-119.61), CVintra: (Getting one CVintra for Cmax, shown above)

2-Run the analysis on two different datasets. One including A and C, the other including B and C.

A, Cmax, 104.24 (85.84-126.57), CVintra: 32.9%
B, Cmax, 95.55 (76.54-119.29), CVintra: 38.0%

Which way to go?

In both cases it is a highly variable drug, widened limits and bioequivalent, Right?

Thank you for your help,
Kind regards,
BRN

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Edit: Merged from a later post; you can edit posts for 24 hours. [Helmut]