heritage
☆    

India,
2018-02-17 07:32
(1436 d 21:39 ago)

Posting: # 18427
Views: 3,597
 

 T>MIC for Anti microbial is sufficient to show therapeutic efficacy [Regulatives / Guidelines]

Hi all

I need one help.

My objective is to replace immediate release formulation one antimicrobial with sustained release formulation of the same antimicribial

Can pharmacodynamic end-point (T>MIC) of Sustained Release formulation establish therapeutic effect and hence waive need to do clinical study? or we have to do a clinical study of Sustained release formulation vs immediate release formulation?
ElMaestro
★★★

Denmark,
2018-02-17 12:11
(1436 d 16:59 ago)

@ heritage
Posting: # 18428
Views: 2,981
 

 T>MIC for Anti microbial is sufficient to show therapeutic efficacy

Hi Heritage,

» Can pharmacodynamic end-point (T>MIC) of Sustained Release formulation establish therapeutic effect and hence waive need to do clinical study? or we have to do a clinical study of Sustained release formulation vs immediate release formulation?

This is a strategy that works for some developers, but mainly in EU. It does require that you know a lot about the ref. product from publications or from PARs and that the regulators you talk to are friendly. It may vary from agency to agency.
I would seek sc.advice for a 10.3 submission in EU, or approach FDA for a dialogue (controlled corr.) for a prospective 505(b)(2) development.

T>MIC in plasma is a good guess, but depending on the ADME caracteristics it may be not-so-well correlated with efficacy. Look for example at Azitromycin. This is an area were the fine distinction between rate and extent of the API being absorbed vs rate and rate of the API becoming available at the site of action seems muy importante.

Seek regulatory dialogue. Lots of it.

Pass or fail!
ElMaestro
heritage
☆    

India,
2018-02-17 14:26
(1436 d 14:45 ago)

@ ElMaestro
Posting: # 18429
Views: 3,027
 

 T>MIC for Anti microbial is sufficient to show therapeutic efficacy

Hi EIMaestro

Thank you for valuable inputs. Do we evaluate T>MIC always in patients or it can be done in healthy vouln.?


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut]
ElMaestro
★★★

Denmark,
2018-02-17 18:13
(1436 d 10:58 ago)

@ heritage
Posting: # 18430
Views: 2,947
 

 T>MIC for Anti microbial is sufficient to show therapeutic efficacy

Hi Heritage,

» Thank you for valuable inputs. Do we evaluate T>MIC always in patients or it can be done in healthy vouln.?

You evaluate it in exactly the population that the regulator is asking for :-)

Pass or fail!
ElMaestro
Helmut
★★★
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Homepage
Vienna, Austria,
2018-02-17 21:27
(1436 d 07:44 ago)

@ heritage
Posting: # 18431
Views: 3,025
 

 Therapeutic Occupancy Time

Hi Heritage,

» Thank you for valuable inputs. Do we evaluate T>MIC always in patients or it can be done in healthy vouln.?

T>MIC (actually tMIC) is called “Therapeutic Occupancy Time” (see this post). That’s a PK metric, not a PD endpoint. We performed such a study (antibiotic, MR vs. IR) a while ago. Be aware that
  • MIC generally is an in vitro concentration. For most antibiotics in vivo MIC is based on a wacky calculation.
  • For  most  (all?) antibiotics there is more than one MIC (different strains of bacteria show different susceptibilities).
@ElMaestro: Forget patients. You will never find ones with the same grade of infection. Parallel design difficult. Crossover impossible.

We performed a crossover in healthy subjects where we had three MICs.
  • Confirmatory: One-sided test for the Occupancy Times (superiority).
  • Exploratory: AUC (two-sided).
  • Descriptive: Cmax (no CI).

Dif-tor heh smusma 🖖
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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heritage
☆    

India,
2018-02-18 07:19
(1435 d 21:52 ago)

@ Helmut
Posting: # 18432
Views: 2,884
 

 Therapeutic Occupancy Time

Hi Helmut

Thank you for your reply

I need to learn three points

1. What should be design and patient population of the study? I found many studies on clinical trials.gov wherein patient was taken.

Can you advice any good articles to read wherein healthy were taken

2. T>MIC study can waive need to do clinical trial?

3. Is there any regulatory guidance available for T>MIC stud?
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