Pharma_88
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China,
2020-01-08 09:07

Posting: # 21067
Views: 3,286
 

 Steady State Bioequivalence Study [Design Issues]

Hello All,

A case of Steady state bioequivalence study in which dose is administered twice daily from Day XX to Day XX. Suppose Day 01 to Day 07 where on day 07 only morning dose will be administered. My question is what is the ideal pre-dose time points required to collect to get Cpd. As per guideline, at least 3 pre-dose samples are required to collect. But as we are administrating Drug twice daily, its is necessary to collect pre-dose for morning and evening both for few days i.e Day 01 (morning evening), Day 04 (morning evening) and Day 07 (Morning)?

Also suggest for t.i.d. administration.

Appreciate your valuable suggestion in this regards.


Edit: Category changed; see also this post #1[Helmut]
Helmut
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Vienna, Austria,
2020-01-09 11:36

@ Pharma_88
Posting: # 21069
Views: 1,109
 

 Pre-dose samples

Hi Pharma_88,

» A case of Steady state bioequivalence study in which dose is administered twice daily from Day XX to Day XX. Suppose Day 01 to Day 07 where on day 07 only morning dose will be administered.

This is only acceptable if you know that there are no circadian differences in PK. Otherwise, you have to administer both doses on day 7 as well and assess the complete 24 hours profile.

» As per guideline, at least 3 pre-dose samples are required to collect. But as we are administrating Drug twice daily, its is necessary to collect pre-dose for morning and evening both for few days i.e Day 01 (morning evening), Day 04 (morning evening) and Day 07 (Morning)?

The idea behind is to assess whether you reached (pseudo-) steady state.* Hence, pre-doses on the mornings of day 5, 6, 7.

» Also suggest for t.i.d. administration.

Similar.


  • At last month’s 4th workshop of the Global Bioequivalence Harmonization Initiative (GBHI) in Bethesda there was a consensus that no statistical test should be performed. Give a table of results, geometric means / CV, and plots.

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Summertime
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Slovenia,
2020-03-26 16:29

@ Helmut
Posting: # 21301
Views: 528
 

 Study design multiple dose stuy - circadian PK

Hi to all.

My question is related to below Helmuts post:

» » A case of Steady state bioequivalence study in which dose is administered twice daily from Day XX to Day XX. Suppose Day 01 to Day 07 where on day 07 only morning dose will be administered.
»
» This is only acceptable if you know that there are no circadian differences in PK. Otherwise, you have to administer both doses on day 7 as well and assess the complete 24 hours profile.

Is this really necessary also for non-pulsatile modified-release forms (especially when efficacy is not compromised due to circadian differences in PK)? I see many challenges in this approach - especially I find it very volunteer unfriendly, as relatively intense blood sampling would be done also during the night.
Helmut, is this your personal opinion what would be the most right thing to do or you came across that demand/opinion form regulatory authorities? Would highly appreciate your explanation.

Thanks in advance,
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