Researcher101
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Egypt,
2020-10-14 08:21
(48 d 12:33 ago)

Posting: # 21997
Views: 534
 

 Multiple dose design Sample size [Power / Sample Size]

Dears, I just wanna know if Steadystate Cmax intrasubject variability will be considered in sample size calculations of multiple dose BE? or just Cmax of single dose?

Also is it in the safe side to estimate sample size based on Cmax single dose not multiple dose?


Edit: Category changed; see also this post #1[Helmut]
Helmut
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Vienna, Austria,
2020-10-14 09:27
(48 d 11:26 ago)

@ Researcher101
Posting: # 21999
Views: 476
 

 CV of Css,max ≤ CV of Cmax

Hi Researcher101,

if you have the CV of Cmax from a MD study that’s best, of course.

» Also is it in the safe side to estimate sample size based on Cmax single dose not multiple dose?

Yes, since generally (I know only one published exception*) variability in steady state is ≤ the one after a single dose.


  • Van Hoogdalem EJ, Terpstra IJ, Krauwinkel WJ, Volkers-Kamermans NJ, Baven AL, Verschoor JS. Multiple dose bioequivalence study with josamycin propionate, a drug with highly variable kinetics, in healthy volunteers. Int J Clin Pharmacol Ther. 1996;34(5):202–7. PMID 8738856.

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Researcher101
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Egypt,
2020-10-14 11:37
(48 d 09:16 ago)

(edited by on 2020-10-19 08:41)
@ Researcher101
Posting: # 22000
Views: 458
 

 Multiple dose design Sample size

Also if Cmax ss within variability is around 20 % and Cmin ss within variability is around 41 % on which one should I depend


Dears, I am asking about the factor we determine the sample size in multiple dose studies? Should I estimate sample size based on intra subject variability of Cmin or Cmax or C tau?

Can I pool the CVs to estimate sample size?


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Ohlbe]

Edit: Post merged with a new (deleted) post of 2020-10-19. Relax; see also this post #9[Helmut]
Helmut
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Vienna, Austria,
2020-10-19 14:17
(43 d 06:37 ago)

@ Researcher101
Posting: # 22030
Views: 347
 

 Sample size based on worst case

Hi Researcher101,

» […] sample size in multiple dose studies? Should I estimate sample size based on intra subject variability of Cmin or Cmax or C tau?

Based on the one with highest variability – if the assumed T/R-ratios are identical. If not, explore various combinations and opt for the worst case. This gives you a safety margin for the other PK metrics.

» Can I pool the CVs to estimate sample size?

Doesn’t make any sense.

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dshah
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India,
2020-10-20 04:43
(42 d 16:11 ago)

@ Researcher101
Posting: # 22033
Views: 315
 

 Multiple dose design Sample size

Dear Researcher 101,

If you have performed any single dose study, its best to perform Superposition as per SmPC/ PI instruction. Then perform the stat at Steady state- you will know the %CV for all the required parameter and then take a call.
Mostly- based on theoretical assumption, the %CV will come less in multi dose for this phenomena.
Regards,
DShah
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