Bioequivalence and Bioavailability Forum

Dear ioanam!

❝ It was a single dose study(only in fasted conditions) and multi- dose study. In this study, the first period of the single dose study was followed by the first period of the steady - state study. The wash out period began after the last dose administered in the steady - state study. The second period was identical with the first one. Is correct this design for the study?

In this case the sponsor obviously tries to kill two birds with one stone

Let's go into the datails - if I got it wright:
In steady state you measure for 24 hours, whereas in single dose your last sampling point is determined by the regulatory requirement to cover at least 80% of AUC_inf (i.e., by the half life of the drug and the LLOQ of the assay).
Therefore the saturation phase for the multiple dose part may only start as early as the time point of the last expected concentration above LLOQ in any of the subjects (otherwise you may jeopardize accurate estimate of AUC_inf in this subject).
Saturation up to steady state and the profile itself is pretty straightforward, but in order to get all drug cleared from the body (assuming accumulation) our washout to the second single dose period generally will be longer than for a 'conventional' single dose design.
Have you ever thought about the blood loss in such a 'design'?
What about statistics? Only if we close our eyes the comparisons for BE will come from 'periods 1&2' - because actually we have 4. BE will be calculated from 1&3 (single dose) and from 2&4 (steady state). We should incorporate this information in the model - and don't ask me about regulatory acceptance
What if one of the two parts fail to demonstrate BE? It will be impossible to 'split' your data...
We are also loosing time: in a multiple dose steady we dont need a washout phase at all; we may directly switch from one formulation to the other.

❝ I know that for extended - release formulations must be performed totally different studies (single dose and multi - dose studies) in different periods. Is this correct?

I would think so - see above