Bioequivalence and Bioavailability Forum • IR versus MR

drcampos
★

Brazil,
2007-03-27 17:17
(7019 d 03:42 ago)

Posting: # 600
Views: 6,896

IR versus MR [Design Issues]

Dear All,

I intend to perform a bioequivalence study between a immediate release formulation (IR) and a modified release formulation (MR). The study will design like that: single dose of MR formulation at time 0 (t=0h) and multiple dose of IR formulation (at time = 0h and 12h). The samples will be colleted considering 3-5 times the half-life of the drug. However, the objective would be to obtain the same bioavailability of the formulations until 24 h.

Considering the pharmacotherapy the IR fomulation is given two times per day (12/12h) and the MR formulation is given once per day (24/24h).

Your insight on this matter would be appreciated.

Daniel Rossi de Campos
Brazil

gagandeep
●

2007-03-29 12:58
(7017 d 08:01 ago)

@ drcampos
Posting: # 601
Views: 5,617

IR versus MR

Post reply

Dear

I suggest you perform the study by the following method:

See the Tmax, Cmax and half-lives of the drugs
Dose the subjects with the MR and choose timepoints as per Tmax and half-life – Plot the timepoints accordingly (keep frequent timepoints near Tmax)
With the BD drug, again plan timepoints accordingly and keep them frequent near each Tmax.
Remember that the timepoints and consequently blood collection for the subjects randomized into BD dosing will be more. Hence take care not to exceed the total volume of blood collection more than your SOP’s / procedures / IRB recommendations
In case you are doing fast and fed studies and for example, if food delays Tmax or changes the slope of the graph of conc v/s time, then you may have to re-adjust timepoints of in fed study, or even add / subtract a couple timepoints.
Your statistician should be prepared well for such project.

Good luck!

Dr. Gagandeep Singh
Head – Clinical Research
BioArc (Alembic Pharma)

hirenpharm ☆ Ahmedabad, 2007-04-01 16:33 (7014 d 04:26 ago) @ gagandeep Posting: # 608 Views: 5,597	IR versus MR Post reply
	Dear, If we design different time points for IR and MR then it can add bias at bioanalytical level!!!!!!

Helmut
★★★

Vienna, Austria,
2007-04-02 01:18
(7013 d 19:41 ago)

@ drcampos
Posting: # 612
Views: 5,605

IR versus MR (not BE!)

Post reply

Dear Daniel!

Just to keep terminology high: it's not possible to demonstrate bioequivalence between MR and IR, because this would imply no differences both in extend and rate (only possible for IR v.s. IR, or MR v.s. MR).

At least for the EU, even if your MR OAD formulation is mimicking an IR formulation given BID, and you succeed with almost superimposable curves, you will have to a lot of stuff to show (food effect [dose dumping!], eventually steady state, and almost for sure a clinical study as well...; for a nice story see this post).

For an overview of work to be done see the European Note for Guidance (especially Section 4 and Appendix 1).

P.S. I agree with Gagandeep's post (we should design sampling schedules to get the highest possible amount of information from the profiles of both formulations).

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gagandeep ● 2007-04-05 19:56 (7010 d 01:02 ago) @ drcampos Posting: # 636 Views: 5,506	IR versus MR Post reply
	Dear Daniel, I forgot to mention in my post (and totally agree with HS) that this cannot be a BE study. This will be a comparative bioavailability study - so make sure you mention the BA word and not BE in the protocol title as well. Gagandeep