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Norah
Junior

Tunisia,
2018-02-20 09:14

Posting: # 18437
Views: 2,842
 

 Diclofenac SR fast or fed state study design [Design Issues]

Hello, I need your advice please for diclofenac SR 75 mg:
should study be conducted in fasting or fed state?
thanks a lot
* Emea guidelines should be followed for me
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2018-02-20 12:45

@ Norah
Posting: # 18438
Views: 2,438
 

 Homework

Hi Norah,

see this post #3. The collection of Guidelines / Guidances is linked in the menu of the Forum.
Details are given in Appendix IV of the EMA’s GL.

Cheers,
Helmut Schütz
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Norah
Junior

Tunisia,
2018-03-09 16:45

@ Helmut
Posting: # 18514
Views: 2,027
 

 Homework

Thank you Helmut :)
xtianbadillo
Junior

Mexico,
2018-03-09 19:31

@ Norah
Posting: # 18518
Views: 2,037
 

 Diclofenac SR fast or fed state study design

» Hello, I need your advice please for diclofenac SR 75 mg:
» should study be conducted in fasting or fed state?

https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm188529.pdf

Active ingredient: Diclofenac Sodium
Form/Route: Extended Release Tablets/Oral
Recommended studies: 2 studies

1. Type of study: Fasting
Design: Single-dose, two-way, crossover in-vivo
Strength: 100 mg
Subjects: Healthy males and nonpregnant females, general population.
Additional Comments:
______________________________________________________________________________
2. Type of study: Fed
Design: Single-dose, two-way, crossover in-vivo
Strength: 100 mg
Subjects: Healthy males and nonpregnant females, general population.
Additional comments:
_______________________________
Norah
Junior

Tunisia,
2018-03-14 11:55

@ xtianbadillo
Posting: # 18535
Views: 1,898
 

 Diclofenac SR fast or fed state study design

Dear xtianbadillo

» Active ingredient: Diclofenac Sodium
» Form/Route: Extended Release Tablets/Oral
» Recommended studies: 2 studies : does it mean that both should be perofrmed??

thanks ____
xtianbadillo
Junior

Mexico,
2018-03-16 15:26

@ Norah
Posting: # 18562
Views: 1,844
 

 Diclofenac SR fast or fed state study design

» » Recommended studies: 2 studies : does it mean that both should be perofrmed??

Yes, you have to perform both studies. There are some recommendations.

1) Two cross-over, One study should be conducted under fasting conditions and the other after-meal intake at a specific time before the administration of the treatment.

2) A study cross-over, with four periods, with four sequences for four treatments. Both the test medication and the reference medicine should be evaluated under fasting conditions and after food intake at a specific time before the administration of the treatment.
Norah
Junior

Tunisia,
2018-04-02 12:22

@ xtianbadillo
Posting: # 18629
Views: 1,628
 

 Diclofenac SR fast or fed state study design

thanks again xtianbadillo!!
nobody
Senior

2018-04-02 14:29

@ Norah
Posting: # 18631
Views: 1,622
 

 Diclofenac SR fast or fed state study design

Your first post:

» * Emea guidelines should be followed for me

...and then somebody posts the FDA guidance and you are happy. Did I miss something?

Kindest regards, nobody
Norah
Junior

Tunisia,
2018-04-02 15:05

@ nobody
Posting: # 18632
Views: 1,611
 

 Diclofenac SR fast or fed state study design

Hello No Body
It is not what I need , but I have to thank him for his reply !!
balakotu
Regular

India,
2018-04-13 08:22

@ Norah
Posting: # 18678
Views: 1,265
 

 Diclofenac SR fast or fed state study design

» Hello, I need your advice please for diclofenac SR 75 mg:
» should study be conducted in fasting or fed state?
» thanks a lot
» * Emea guidelines should be followed for me

Dear Norah,
"Diclofenac sodium 75 mg SR tablets" is modified release formulation.

Please be noted that, as per EMEA, we need to consider fasting, fed and multiple dose studies for Modified release (ER, SR, MR) formulations.

Please find the below statement from EMA guidelines on modified release formulations. Page number 18 & 19. {Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1)}

6.1.1. Studies generally required to demonstrate bioequivalence:
a single-dose fasting study comparing test and reference drug product.
a single-dose fed study using a high-fat meal comparing test and reference drug product.
a multiple-dose study comparing test and reference drug product.


We can skip the multiple dose study by showing a low extent of accumulation for the formulation. We need to show the mean AUC(0-tau) after the first dose covers more than 90% of mean AUC(0-inf) for both test and reference in fed study. (fed condition is the SmPC recommendation).
The dose is One tablet once or twice daily.
So we need to consider 12 hours as the tau (dosing interval).
If you show the mean AUC0-12 is more than 90% of the mean AUC0-inf for both test and reference in fed study, you can skip multiple dose study.

Ref: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/11/WC500177884.pdf
https://www.medicines.org.uk/emc/product/2661/smpc
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