Initial dose and design issues abridged submission daily ER vs BID IR [Design Issues]

posted by alejandro_jo1990 – Spain, 2022-09-15 17:35 (530 d 18:21 ago) – Posting: # 23299
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Dear All,
When it comes to comparing an extended release compound administered once a day to the inmediate release compound (same active compound of course), Would I need to determine the initial dose and dosing interval based on pre-clinical data? (animal models?). I guess that taking the total daily dose of the IR x 2 as the daily dose for the ER wont be a nice approach as nothing can guarantee not dose dumping or that (even without dunping) that the release of the formulation with dampen the Cmax. Much risk for a FIH right? We can even assure qd is the appropriate interval.

The guideline also states the necessity of a clinical study, if a surrogate is well correlated to clinical outcomes would a non-inferiority trial with that PD endpoint enough? Even more than that, providing that theres a strong correlation between exposure and PD response, would a denonstration for BE regarding the total 24h AUC of the IR BID vs ER qd and demonstration for non-superiority of Cmax enough?. No accumulation is expected, hence I think single dose might be sufficient.


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