Bioequivalence and Bioavailability Forum

Hi to everybody.

RSABE and ABEL came to aid in studies of HVDs/ HVDPs, but what must we do when we are dealing with a fixed dose combination (FDC) that has, for instance, 3 drugs with different PK, and consequently different blood sampling schedule, and one of the drugs is a HVD?

Take Clorpheniramine + Phenylephrine + Paracetamol as a example. We are worried with Phenylephrine's ISCV and want to use the ABEL approach for it, but for the other 2 drugs we don't feel that there is need for that. If I use a replicated design, even a 3-period one, the sampling schedule is very compromised. In Brazil we have a limit of 530mL of blood per study, so no more than that can be withdrawn from the subjects in the entire study.

So my question is: is it possible to not use the replicated samples for the other 2 drugs and apply conventional ABE for them, and consider the replication only for the HVD? Does that make sense? For me this seems a bit bizarre and questionable, in ethics and in GxP. Other option would be to use Balaam's 4x2 design, but I don't think that someone has budget for that...

THX in advance.

Lucas