Bioequivalence and Bioavailability Forum

Hi VR,

❝ So, Here we performing on Healthy male subjects under fasting condition, that so, is it mandatory for every generic drug (Eg - our insulin test and reference products) should conduct on under Healthy subjects under fasting condition ?

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❝ Is this study kind of assessing the dosage regimen, efficacy, ADR on Healthy subjects ?

I can't tell from the info you have given what type of study you are doing, but I think you are saying you are comparing two insulins. It sounds like a BE study.
In that case you are taking blood samples every now and then, probably after the subjects have been given the insulin as an s.c. injection. In these blood samples you measure insulin levels.
Next, you draw a graph showing the concentration of one insulin as function of time after injection, and on the same graph you draw the other insulin. The two are bioequivalent if the two curves are sufficiently close to each other by some well-defined criteria. The criteria define sameness of the rate and extent of the insulin getting from the site of injection into the blood stream.

And it is funny, because in fact it is not so difficult to take these samples that are used to make those graphs. 95% of all the tedious work with a clamp study of that type, is the clamp itself which is only used to keep the subject safe, but not so much used to compare the two insulins. It is almost unfair (but let it be said, if one insulin works much better than the other, then possibly you will see a different need for glucose; things are usually not that clear in practice).

So, I think, without being absolutely sure that the answer is, that you are mainly studying if the rate and extent of absorption is similar for two products. That is a primary purpose. You will always in your protocol see some secondary purpose such as assessment of safety or something.
Healthy volunteers: Much preferred over patients, if possible. Safer, much easier, fewer AEs. Often a comparison of rate and extent done in volunteers can be extrapolated to patients. Technically, it does not mean rate and extent is the same for a given insulin in patients and in healthy volunteers. Rather it means that if the rate and extent is similar for insulin 1 and insulin 2 in volunteers, then it can quite safely be assume to also be similar in patients.
Fasting: When the subject is fasting as the clamp is started you have much better control over the glucose levels. It can be totally controlled with the glucose infusion. It would be different if one subject has been eating snickers right before dosing. Another subject has been eating something else, but can't remember what it was. A third subject hasn't eaten, and so forth. It is completely standardised when you are using fasting subjects. The only glucose you see in the body is the glucose from the clamp, you can complete keep the subject within a tolerable window.