Flashback [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2012-04-05 16:10 (3580 d 13:03 ago) – Posting: # 8386
Views: 8,482

Hi John!

» This just popped into my head (flashback... Nightmare, whatever you called it)...

For me – flashback. We performed a pilot study of a drug with a nice average [sic] half-life of ~50 hours, sampling up to 216 hours (since truncated AUC wasn’t common at that time), washout 2 weeks. No predose concentrations… The pivotal was a 6×3 in 36 subjects, but:Result: We measured pre-dose values (maximum 7.8% of Cmax) in 54% of samples of periods 2 & 3 (none in period 1). Since we had a blinded plausibility review in place we were able to come up with a statistical amendment while analytics were still running:Results:Lessons learned: Never base the washout on mean-values (large studies not even on x±SD) and think twice if you improve the analytical method too much. ;-)

P.S.: The product was approved based on this study in the EU in 2002 and by the FDA in 2003.

» Should the lab adjust the concentration profile to remove the residual levels caused by the pre-dose concentration???? ie. using the t1/2 and determine the amount of pre-dose concentration remaining throughout the timepoints and subtract it from the respective concentrations.

See above. I cannot imaging that any regulatory agency would accept this (any more).

» I remember one lab doing this and they said it's part of their SOP...

Referring to an SOP is alway the worst (pseudo-)justification I can think of.

“Hey, let’s jump from the cliff!” Lemming’s SOP

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Helmut Schütz

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