Brus
☆    

Spain,
2020-03-27 17:22
(343 d 12:50 ago)

Posting: # 21303
Views: 1,579
 

 Meets primary objective but not secondary objective [Study As­sess­ment]

Dear colleagues,

I tell them my case if they can help me:

We have carried out a bioequivalence study with a drug that, due to its metabolism, it generates various metabolites in the human body. In the protocol, we specified bioequivalence in one metabolite as the primary objective, and bioequivalence of two other different metabolites as a secondary objective.

What happens if we meet the primary objective but not the secondary one?

Thank you very much
kratos
☆    

India,
2020-03-31 03:17
(340 d 03:55 ago)

@ Brus
Posting: # 21309
Views: 1,096
 

 Meets primary objective but not secondary objective

Hi Brus,

Many a times the metabolite has different pharmacokinetics than that of the parent drug.
It is common to design a study only with the parent drug in mind. With timepoints around the Tmax of the parent drug, ignoring the metabolite PK.
In such a case, the design is more in favour of a proper evaluation of the parent drug !
Also sample size calculation is often performed considering the ISCV of the parent drug (in case it is the BE determinant).
The supportive data swings by, not being 'appropriately' evaluated.
It all depends on the regulatory requirement for the application.
FDA verifies point estimate values for supportive data; not the ANOVA, so sample size would not be so significant.
EMA on the other hand, for generics, the preference is always to measure the parent when feasible.
Only in case of a rapid conversion - the major metabolite is considered. . .
It would ultimately depend on the goals of your application.
Achievwin
★    

US,
2020-03-31 21:09
(339 d 10:03 ago)

@ Brus
Posting: # 21310
Views: 1,068
 

 Meets primary objective but not secondary objective

As far as Bioequivalence study is concerned there is only a primary objective (no secondary objectives) which is specified in the published BE guidance (in case of FDA), BE acceptance criteria is specified by Regulatory bodies per product. In the absence of a published guidance use the following criteria

1. Fasted and Fed studies
2. BE criteria must be met for 1) Parent drug (unless is not detected) and major circulating active metabolite (it needs to be more than 20% of the parent drug or so),
3. establishing BE for inactive metabolites if they are not major circulating metabolites is only a supportive data)

Hope this helps.
kratos
☆    

India,
2020-04-01 02:00
(339 d 05:12 ago)

@ Achievwin
Posting: # 21312
Views: 1,058
 

 Meets primary objective but not secondary objective

Totally agree.
I cringe when some CROs state 'monitoring subject safety' as a secondary objective in a Bioequivalence study !
Achievwin
★    

US,
2020-04-06 19:41
(333 d 11:31 ago)

@ kratos
Posting: # 21317
Views: 959
 

 Meets primary objective but not secondary objective

Monitoring subject's safety is oxymoron in Healthy subjects study. In patient studies subjects safety foes into Medical History... still it won't secondary objective at the most it is a supportive information. You don't make BE decisions based on Clinical Endpoint or PK Bioequivalence
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