A prospective, randomized, cross-over, single-blind, placebo-controlled study to assess the pharmacodynamic effects, pharmacokinetics and safety and tolerability of one dose of 30 mg ulipristal acetate (UPA) followed by the administration of 20 days of 75 µg desogestrel (DSG)

In recent years, a new *morning-after pill* or emergency contraceptive (EC) has
been available throughout Europe known as ellaOne® and known as ella® in the
USA. EllaOne® has been available for use in Europe since October 2009 and 2010
in the USA. The medicine that is in ellaOne® is called ulipristal acetate (UPA)
and it can be used for emergency contraception to prevent pregnancy by delaying
the release of the egg from the ovary. UPA works by blocking the action of one
of the hormones from the ovary, called progesterone.
Progestin-only pills (POP) are used by women as regular hormonal contraceptive.
The mechanism of action of most POPs is based on the effect of the progestogen
on cervical mucus (fluid secreted by the cervix which changes its consistency
throughout the cycle), making it unfavourable for sperm penetration at the time
of ovulation.
Because UPA blocks the action of the hormone progesterone, there is a
theoretical concern that it might affect the POP action and maybe make the pill
less effective. We want to study the potential interaction between UPA and POP
when treatments are administered sequentially. The study will also assess the
contraceptive effect of POP in terms of cervical mucus for women using POP as
regular hormonal contraceptive immediately after UPA in the same cycle.

The aim of the present study is to assess the contraceptive potential of the
association of UPA 30 mg single dose and desogestrel 75 micrograms for 20 days.
The study will also assess the potential possible interaction, (in terms of
ovarian activity measured by hormonal levels and vaginal ultrasounds and in
terms of cervical mucus measured by evaluation of the WHO score,) between UPA
and DSG when administered sequentially at mid-follicular phase. Finally, the
study will also assess the contraceptive effect of DSG in terms of cervical
mucus (measured by evaluation of the WHO score) for women using DSG as
continuing contraception immediately following UPA in the same cycle and the
potential pharmacokinetics interaction between UPA and DSG as well as safety
and tolerability of the treatments

A randomized, cross-over, single-blind, placebo-controlled study

The study will start with a screening visit. During the inclusion visit
standard medical assessments including safety laboratory tests (blood draw), a
physical examination and a vital signs measurement will be performed. In
addition a standard gynecological examination will be performed including a
cervical smear (if not done in the last 11 months) and TVUS assessment.

After the subject passes all above mentioned tests, the subject will be
enrolled in the pre-treatment phase. When the dominant follicle reaches 14 mm
and is < 16 mm, the subject will be enrolled. During the study the subjects
will receive 2 medication formulations, will be asked on a regular basis for
possible side effects, blood will be drawn for safety and PK/PD measurements,
cervical mucus will obtianed and examined regularly 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 and the vital signs will be checked

1.Subjects having a blood test may experience discomfort and bruising and
possibly (rare) an infection at the needle site, or anemia. The subject will
have her blood sampled no more than a maximum of 60 times during the entire
study. The total quantity of blood sampled during the entire study will be no
more than approximately 545 mL.
2. The most common adverse reactions (>=5%) in the clinical trials with
ulipristal acetate 30 mg were headache, abdominal pain, nausea, dysmenorrhea,
fatigue and dizziness.
3. The most commonly observed undesirable effects of desogestrel 75µg are
bleeding irregularity reported in up to 50% of women, vaginal bleeding may also
be of longer duration. Other undesirable effects in the clinical trials with
desogestrel (> 2.5%) were acne, mood changes, breast pain, nausea and weight
increase.
4. The subject may experience irregular bleeding or spotting.
5. Vaginal ultrasounds and collect of cervical mucus have no known risk, but
may be associated with discomfort.