Bioequivalence and Bioavailability Forum • Scaling of Cmin

Scaling of Cmin [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2014-12-10 19:40 (3423 d 11:38 ago) – Posting: # 14051
Views: 13,391

Dear Dan,

I think that your example is a fully replicate design (i.e., RRTT|TTRR) indeed. Just substitute drug1 with R and drug2 with T and you’ll get the first of the two sequences from above. Of course you have to modify the code given in EMA’s Q&A (for RTRT|TRTR) accordingly. But that’s an easy task.
This concept would work for all PK metrics. Coming back to the subject line (and which was discussed in Bonn): Scaling only C_min without the need of sampling four full profiles.

treatment dose

    R       1

    R       …

    R       n ⇒ profile

    T       1

    T       …

    T       n ⇒ profile

On profile days you have two values of C_min. One prior to dosing and another one at τ. Now the stats become interesting. You would need to introduce an additional code (e.g., “replicate”) to distinguish these two values because they are sampled from the same period(s). I’m working on it. EMA’s preference of an all-fixed model is nasty. My current setup is: Sequence+Subject(Sequence)+Treatment+Replicate+Treatment(Replicate)+Period

PS @Anders: Sorry for the nesting. I know, I know.

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Helmut Schütz

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Complete thread:

Type of study in modified release formulation EMEA Compliance 2014-03-13 09:43 [Regulatives / Guidelines]
- Type of study in modified release formulation EMEA nobody 2014-03-13 09:52
- Type of study in modified release formulation EMEA fno 2014-03-13 11:16
  - Type of study in modified release formulation EMEA kumarnaidu 2014-11-27 11:02
    - Type of study in modified release formulation EMEA nobody 2014-11-27 11:37
      - Type of study in modified release formulation EMEA kumarnaidu 2014-11-27 12:53
        
        Scaling of Cmin Helmut 2014-11-27 13:47
        
        Scaling of Cmin kumarnaidu 2014-11-27 15:12
        Scaling of Cmin kumarnaidu 2014-12-05 06:03
        
        Steady state kumarnaidu 2014-12-10 11:15
        
        Steady state nobody 2014-12-10 17:04
        
        Scaling of Cmin Dr_Dan 2014-12-10 17:21
        
        Scaling of CminHelmut 2014-12-10 18:40
        
        Scaling of Cmin d_labes 2014-12-11 13:09
        
        Scaling of Cmin Helmut 2014-12-11 14:53
        
        Scaling of Cmin VStus 2017-02-03 13:04
        
        Scaling of Cmin zizou 2017-02-03 13:49
        
        Scaling of Cmin VStus 2017-02-03 15:37
        Scaling of Cmin VStus 2017-02-06 08:55