SR formulations - no MD study? [General Statistics]
Dear hirenpharm!
First of all have a look at Imran's post about metrics in steady state.
Single dose parameters are AUClast, AUCinf, and Cmax (although depending on the drug and the type of formulation other parameters like Cmax/AUC, HVD, and MRT may be of interest).
Do I get you right:
AUClast and AUCinf passed, whereas AUC truncated at 24 h did not? This is an interesting phenomenon I never came across before!
Based on what?
Do you mean that if you do not expect any accumulation, there is no need for such a study?
Yes, but I strongly would suggest a scientific advisory meeting beforehand.
Just to give you an example, we tried to get around a multiple dose study for a formulation with following properties:
OK, the simple one: it's against the guidelines - at least in many countries.
The rationale for a multiple dose study is not only to show BE in steady state, but to get information about potential problems (i.e., even if you have demonstrated no food effect in single dose, and dose dumping is a rare event, you have a higher chance to 'see something' in steady state).
❝ If a single dose BE study of a SR product Vs SR product...we find AUC0-last failing but AUC 0-T(Tau)(say 0-24 hrs) passing and Cmax and AUC0-inf is also passing.(fast and fed)…
First of all have a look at Imran's post about metrics in steady state.
Single dose parameters are AUClast, AUCinf, and Cmax (although depending on the drug and the type of formulation other parameters like Cmax/AUC, HVD, and MRT may be of interest).
Do I get you right:
AUClast and AUCinf passed, whereas AUC truncated at 24 h did not? This is an interesting phenomenon I never came across before!
❝ …and no need for steady state.
Based on what?
Do you mean that if you do not expect any accumulation, there is no need for such a study?
❝ Can be seek TGA approval for the study?
Yes, but I strongly would suggest a scientific advisory meeting beforehand.
Just to give you an example, we tried to get around a multiple dose study for a formulation with following properties:
- MR mimicking two IR doses with tau = 4 h
- half life of the drug 3 h
- no drug above LOQ in the majority of subjects at 12 h
- no drug above at LLOQ in any subject at 24 h
- SPC states OAD administration only
- no accumulation reported in the literature both for IR (tau = 4 h), and another MR formulation
❝ Which objections are anticipated?
OK, the simple one: it's against the guidelines - at least in many countries.
The rationale for a multiple dose study is not only to show BE in steady state, but to get information about potential problems (i.e., even if you have demonstrated no food effect in single dose, and dose dumping is a rare event, you have a higher chance to 'see something' in steady state).
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- SR formulations hirenpharm 2007-01-20 10:05
- SR formulations - no MD study?Helmut 2007-01-22 19:09
- SR formulations - no MD study? hirenpharm 2007-01-23 18:13
- SR formulations - no MD study? Helmut 2007-01-23 18:32
- SR formulations - no MD study? hirenpharm 2007-01-23 18:13
- SR formulations velupharm 2007-01-23 12:38
- bioanalytics (LLOQ) Helmut 2007-01-23 19:59
- bioanalytics (LLOQ) velupharm 2007-01-24 05:36
- bioanalytics (LLOQ) Helmut 2007-01-24 12:40
- bioanalytics (LLOQ) joyjac 2007-05-22 02:13
- bioanalytics (LLOQ) Ohlbe 2007-05-24 23:02
- bioanalytics (LLOQ) joyjac 2007-05-22 02:13
- bioanalytics (LLOQ) Helmut 2007-01-24 12:40
- bioanalytics (LLOQ) velupharm 2007-01-24 05:36
- bioanalytics (LLOQ) Helmut 2007-01-23 19:59
- SR formulations - no MD study?Helmut 2007-01-22 19:09