A phase I, mono-center, randomized, placebo and comparator controlled, single blind, rising dose, clinical study to determine single dose pharmacokinetics, pharmacodynamics, safety and tolerability of four doses of FSH-GEX* according to adaptive design (25, 75, 150 and 300 IU) administered subcutaneously in healthy pituitary-suppressed female volunteers

The aim of the current study is the pharmacokinetic and pharmacodynamic
characterization of a single dose administration of four doses of test compound
in healthy pituitary-suppressed female volunteers, in comparison with two
marketed comparator products

- To assess the safety and (local) tolerability of test compound following
single rising dose administration by subcutaneous injection
- To determine FSH pharmacokinetic parameters including Cmax and AUC0-last of
test compound following single rising dose administration
by subcutaneous injection.
- To assess the pharmacodynamic effect of test compound following single
rising dose administration by subcutaneous injection as
determined by Estradiol (E2) and inhibin B concentrations and ovarian
follicle size, as determined by transvaginal ultrasonography (TVUS)

This is a phase I, single blind, placebo and comparator controlled, randomized,
single dose study in healthy adult female volunteers at 4 different dose
levels. There will be one cohort of 18 subjects. This cohort has a three-period
design and each volunteer will receive 3 successive dose levels during period
1-3

The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), an alcohol breath test, urine drug screen, a physical
examination, ECG and a vital signs measurement will be performed. In addition
standard gynecological test will be performed including a cervical smear and
TVUS assessment.

After the subject passes all above mentioned tests, the subject will be
enrolled in the synchronization phase. On day -3 till day -1 there will be a
pill-free interval. On day 1 till day 60 the subject will be pituitary
suppressed using Marvelon®.

During study the subjects will enter the clinic, will receive 3 medication
formulations, will be asked on a regular basis for possible side effects, blood
will be drawn for safety and PK measurements and the vital signs will be
checked regularly during the 3 confinement periods. During the outpatient
periods, the subject will return in regular intervals. During these visits the
subjects will be asked for possible side effects, blood will be drawn for
safety and PK measurements, the vital signs will be checked and the follicle
sizes will be measured using TVUS regularly.

Finally a follow-up examination will be performed. During this visit the
subjects will be asked for possible side effects, blood will be drawn for
safety, the vital signs/ECG will be checked and a physical examination will be
conducted.

FSH-GEXTM has not been tested in humans. The side effects of the active
ingredient of FSH-GEXTM is expected to be the same as the side effects reported
for the comparator Gonal-F® and Bravelle®.

The most common side effects reported for both Gonal-f® and Bravelle® are:
ovarian cysts, headache and local reaction at the injection site (pain,
redness, bruising, swelling and/or irritation). Following multiple-dose
treatment with Gonal-f® a condition called OHSS (Ovarian Hyper Stimulation
Syndrome) can occur. The occurrence of this syndrome during this study is
unlikely, because only single doses and no other drugs are given in this study.
The syndrome is characterized by large ovarian cysts. First symptoms are pain
in the lower abdominal region, possibly in combination with nausea, vomiting
and weight gain. In rare cases of OHSS, serious complications may occur.