Rules acc. to Health Canada [Outliers]

posted by Helmut Homepage – Vienna, Austria, 2019-02-05 16:24 (602 d 01:32 ago) – Posting: # 19872
Views: 4,274

Hi ElMaestro,

THX for your nice words!

» yes it was meant to indicate that [:blahblah:].

Yep, that’s what I assumed as well.

» However, I don't think they are always enforcing it that way.

Shall I cross fingers?

» After all, rate is not the same as extent and vice versa.

Xactly!

» But does it make a big difference? Exclusion changes little in your case since it was a pilot …

No problems with this one. I’m worried what will happen in the pivotal study.

» … and you will need to consider the sample size and relevance of the CV and PE sampled in the pilot when planning the pivotal in any case.

But that’s the point! This one subject drives the PE to 110% and with a CV of ~50% I end up with ~200 subjects in a 2×2. OK, for HC (and even for the EMA cause it’s a MR) I could apply reference-scaling. 28 subjects in a 2×4. Fine, but the pivotal is a little bit tricky (5 arms already, don’t ask me why). Hence, I don’t want to go there.

» If Cmax and AUC were more or less normal for the subject, …

T/R of Cmax 1.115 and of AUC0–t 1.036…

» … then in all likelihood she munched the medication as directed to and what you saw is populations, products and random happenings at work.

Oh dear! There were formulation changes (plural!) which were acceptable to be supported by dissolution similarity on this side of the pond. AFAIK, this stuff is marketed in ~50 countries. So far, so good. Rules are different. For one of the changes in CAN one would need a BE study. Hence, a lot of stuff to do. The original application was a hybrid (two clinical studies). In order to bridge to the clinical stuff HC wants a BE study of the current formulation against the “old” one.
When looking at the individual curves I would say that the current formulation is closer to the originally aimed target profile. In this subject the old formulation looks bad in the first couple of hours. That’s my problem.

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Helmut Schütz
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