Bioequivalence and Bioavailability Forum

Dear Pash!

❝ 1. Our formulation is IR formulation, but the reported Tmax is around 6-10 hours.

So I assume that rapid onset most likely is neither a clinical claim nor related to AEs. Assessment of t_max is not required.

❝ 2. […] Will it be useful to establish any correlation between adverse events with the plasma concentration data and may be used to rule out formulation performance as the reason of adverse events?

Exactly (see here). Sometimes even a subpopulation of ultraslow metabolisers turn up. See the end of this post.

❝ then what about it's applicability for subject who dropout due to personal reason?

You never know. Sometimes volunteers don’t report AEs and withdraw consent “for personal reasons” fearing that otherwise they won’t be included in future studies. We once performed a multiple dose PK interaction study on orphenadrine where a volunteer dropped out after the 4^th dose. No AEs reported, but trough values were rising significantly faster than in any other subject of the study and would have lead to 10fold higher concentrations in steady state…

❝ […] as USFDA does not require analysis of such dropout subjects.

Here I fully agree with EMA’s position.