alejandro_jo1990
☆    

Spain,
2022-09-15 17:35
(1029 d 03:07 ago)

Posting: # 23299
Views: 2,465
 

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

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.

Thanks!
Alex
UA Flag
Activity
 Admin contact
23,430 posts in 4,931 threads, 1,679 registered users;
57 visitors (0 registered, 57 guests [including 10 identified bots]).
Forum time: 20:43 CEST (Europe/Vienna)

To know that we know what we know,
and to know that we do not know what we do not know,
that is true knowledge.    Nicolaus Copernicus

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5