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dr.who
Junior

Macedonia,
2018-06-27 22:27

Posting: # 18983
Views: 853
 

 Flecainide- NTID [Design Issues]

Nice to meet you all since it is my first time writing on the forum.

My question is related to Flecainide. In the available literature data it is stated that flecainide is a NTID. As per the EU Guideline for BE in the case of NTID the limits are tightened, but no available PAR present a BE for flecainide with tightened limits. Also except Canada no other region have a specific list for NTIDs and for EU it is stated that is evaluated on case by case. What is your experience in design a BE of Flecainide, should the recommendation for NTID design be followed or a standard BE study design is acceptable.

Thanks.
ElMaestro
Hero

Denmark,
2018-06-27 22:39

@ dr.who
Posting: # 18984
Views: 735
 

 Flecainide- NTID

Hi dr.who,

The classical acceptance range is mentioned explicitly here.
Not NTID as I see it.

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
dr.who
Junior

Macedonia,
2018-06-27 23:32

@ ElMaestro
Posting: # 18985
Views: 721
 

 Flecainide- NTID

Thanks for the feedback.

Yes,you are right. All availabe PARS show BE with standard acceptance limits.

But, the originator SmPC states that flecainide is NTID:
"Flecainide as a narrow therapeutic index drug requires caution and close monitoring when switching a patient to a different formulation."

https://www.medicines.org.uk/emc/product/829/smpc

Also, I found this study which consider the NTI for flecainide and regulatory requirements per region.\
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412688/
The Outlaw Torn
Regular

Europe,
2018-06-28 08:57

@ dr.who
Posting: # 18987
Views: 687
 

 Flecainide- NTID

» Thanks for the feedback.

» Also, I found this study which consider the NTI for flecainide and regulatory requirements per region.\
» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412688/

Interesting paper. Funded by Meda Pharmaceuticals. Hmmmmm. :-D

As a pharmacist, I've always categorized flecainide as an NTI. But I've had no exposure to it while in my pharma life. Had I drawn up the protocol (without seeing any PARs), I'd have been tempted to use narrowed CIs. Having seen the PARs, I'm no longer sure. The problem with Europe is that they don't abide by precedent as a principle like the US does (though we always mention it when we have a precedent; you know, put the pressure on the authorities to find a way to reject it). Anyway, I would likely write up the protocol with standard CIs and reference the PARs you've found, and go from there. If the authorities point out the fact that flecainide is an NTID, point them back to the PARs; volley back and forth until someone blinks (usually you). Then provide them the data with narrowed CIs at day 106. Looks like it displays low variability from the UKPAR, so you're likely fine with either CIs.
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