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dear all ,
i would be glad to know the inclusion criteria of human volunteers
for the bioequivalence study of ethinyl estradiol. is it anyway
allowed to include healthy male volunteers in the study. also i want
to know the influence of the day of the menstrual cycle for the study
initiation.
thanks in advance
velli
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The following message was posted to: PharmPK
Dear Velli,
In my knowledge, rather than female volunteers, male volunteers would
be ideal for this. Endogeneous estrogen in female sublects probably
will make this to complicated.
Regards,
Dr Suhas
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Dear Velli,
I think I disagree with Dr. Suhas, because as per the principles of
BA/BE studies, subjects should be of the population for which the drug
is intended. That's why, FDA nowadays recommends to include both female
and male and also older age group (kindly check the guidelines). So in
your case, Ethinyl Estradiol is mainly indicated in female population
and you have to do BE study in female subjects only.
Regarding the inclusion criteria; you can have the standard criterias
such as post menopausal women or subjects practicing non-harmonal
contraceptive methods. And regarding menstruation, since it is a normal
physiology and moreover it can provide you a real situation, no harm in
including them (consider the health status during those time. It should
not lead on to unwanted withdrawals).
Hope this will help you.
More inputs will be appreciated.
Regards
Joseph
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The following message was posted to: PharmPK
Dear Velli,
If you are planning for FDA submission, then what Mr. Joseph has
suggested is absolutely correct. however if healthy female volunteer
are involved, care should be taken to detect endogenous estradiol
level (say you can take 3 Pre dose samples) and washout should be 28
days.
For EMEA submission, it is acceptable to enroll male as well as
female volunteers.
For canadian submission, it is acceptable to enroll male volunteers
only.
Regards,
Hitesh
Shah
Manager-
Clinical
Macleods Pharma ltd
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The following message was posted to: PharmPK
All:
Please note that the following
1. ethinyl estradiol (EE) is a synthetic hormone and is not naturally
occurring so you do not need to take multiple pre-dose concentrations
for endogenous levels as there are none (unless of course the volunteer
is currently taking oral contraceptives containing EE, in which case
they should never have been enrolled in the study)
2. The T1/2 of EE is around 20 hours so a 2 week wash-out is sufficient
but participants should be warned it may disrupt their menstrual cycle.
3. Oral contraceptives are only labeled for use in females. If you start
dosing males with this you will be using the product off-label and you
should consider the regulatory rules and potential legal liabilities of
dosing a population (males) for whom use of this product is not
indicated.
4. We have performed many oral contraceptive BE studies for
US/Canadian/European Submission. All have been conducted in healthy
young females.
Chris Hendy PhD
Novum Pharmaceutical Research Services
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