Relevance of Cτ,ss [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2019-12-20 12:46 2a02:8388:6bc2:ce80:6c4e:e4df:42f4:6510 – Posting: # 21008
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Hi Biostats,

» As per the EMEA definition …

The EMEA lost its second E in 2005. ;-)

» … of Ctau,ss, Ctau,ss is the Concentration at the end of the dosing interval at steady state.

Correct.

» I want to know the significance of Ctau,ss values in steady study?

Required acc. to the GL.
If you compare formulations with different release rates (say CR vs. IR) that’s a hybrid application in the EEA and therapeutic studies might be waived under certain circumstances (see the GL Section 5.2.1).

» What is the interpretation of Ctau,ss?

Good question. In the current regulatory thinking BE is a comparison of the biopharmaceutical performance of formulations (release tested in human “test-tubes”). Similar PK profiles in healthy subjects are assumed to give similar therapeutic responses in patients.
However, this approach mixes up PK with PD, i.e., assumes that Cmax,ss is a measure of safety and the extent of absorption a measure of the effect. Here Cτ,ss enters the scene. Whereas Cmax,ss is believed to be related to toxicity, Cτ,ss is believed to be related to some kind of “minimum required effect”. Hence, an alternative approach to testing equivalence of Cmax,ss and Cτ,ss is the so-called “bracketing approach”, where you perform one-sided tests (non-superiority of Cmax,ss and non-inferiority of Cτ,ss). For an example see there.

Cheers,
Helmut Schütz
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