Mahesh M
★    

India,
2016-05-30 11:42
(2859 d 04:18 ago)

Posting: # 16370
Views: 5,421
 

 multiple dose study [Design Issues]

EMA Published PAR regarding Metformin prolonged release tablet

14 May 2016 | Yaltormin SR 500 mg, 750 mg and 1000 mg Prolonged Release Tablets (metformin hydrochloride) - PL 29831/0655-0657; UK/H/5957/001-3/DC (1640Kb)

As per this PAR Applicant performed 5 BE study
1) 1000 mg Fasting
2) 1000 mg fed
3) 1000 mg fasting multiple dose study
4) 750 mg
5) 500 mg fed

As per SPC “No accumulation is observed after repeated administration of up to 2000mg of metformin as prolonged release tablets then why applicant performed multiple dose study?

As per PIL “You should take Glucophage SR with or immediately after food.” But applicant performed multiple dose study under fasting condition not under fed condition?

Kindly share your thoughts on that?

Regards
M


Edit: PAR linked. [Helmut]
Helmut
★★★
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Vienna, Austria,
2016-05-30 15:37
(2859 d 00:23 ago)

@ Mahesh M
Posting: # 16371
Views: 4,754
 

 1999 Note for Guidance?

Hi Mahesh,

❝ As per SPC “No accumulation is observed after repeated administration of up to 2000mg of metformin as prolonged release tablets then why applicant performed multiple dose study?


See this thread. We don’t know when the studies supporting this application were performed. According to the NfG of 1999 multiple dose was mandatory – unless you convinced regulators of the opposite (scientific advice, etc.). The current GL – which allows waiving the multiple dose study under certain conditions – came into effect on 1 July 2015.
Low accumulation indeed: “Out of 66 [33 Subjects × 2 periods] possible values, only 27 values were plausible, rest were BLQ and therefore Cτ,ss was not acceptable and hence, not considered for bioequivalence equation.”

BTW, as usual in Indian studies the – irrelevant – “post hoc power” is wrong. Given these numbers in the PAR the assessors’ knowledge appears in a bad light.

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Mahesh M
★    

India,
2016-05-31 15:50
(2858 d 00:10 ago)

@ Helmut
Posting: # 16374
Views: 4,542
 

 1999 Note for Guidance?

Dear Helmut

Thank you so much for your response.

As per PIL “You should take Glucophage SR with or immediately after food.” But applicant performed multiple dose study under fasting condition not under fed condition?

Regards
M
Helmut
★★★
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Homepage
Vienna, Austria,
2016-05-31 16:07
(2857 d 23:53 ago)

@ Mahesh M
Posting: # 16375
Views: 4,631
 

 Ask the applicant

Hi Mahesh,

❝ As per PIL “You should take Glucophage SR with or immediately after food.” But applicant performed multiple dose study under fasting condition not under fed condition?


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Mahesh M
★    

India,
2016-06-01 10:45
(2857 d 05:14 ago)

@ Helmut
Posting: # 16376
Views: 4,531
 

 Ask the applicant

Dear Helmut,

Thank you so much for your kind information, I go through all available metformin PAR in public domain 3 Applicant performed multiple dose study under fed condition and two under fasting condition (most recently published PAR ) That’s why I would like to discuss the same on Form. And same happened with dipyridamol XR “As per SPC it recommended under fed condition but as per available PAR applicant performed multiple dose study under fasting condition.

Regards
M
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