A prospective, randomized, double-blind parallel-arm, placebo-controlled study to assess the effects on ovarian activity of a combined oral contraceptive pill when preceded by the intake of ellaOne® (ulipristal acetate 30 mg) or placebo.

In a Cochrane review women who had further episodes of intercourse in the same
cycle as emergency contraception (EC) use had a two- to three-fold higher risk
of pregnancy (Cheng, 2008). This raises the importance of initiating a regular
contraception immediately after EC is used -a practice known as *Quick start*.
Since ulipristal acetate (UPA) is a progesterone receptor modulator, there is
concern that quick starting after UPA could alter the effectiveness of hormonal
contraception and vice versa.

The Clinical Effectiveness of the Faculty of Sexual and Reproductive Healthcare
(FSRH) advises 14 days of additional barrier methods if women are quick
starting the combined oral contraceptive pill (COCP) after using ellaOne® (FSRH
2010). The FSRH also advises that for women who start routine use of the COCP
at any time in cycle other than within the first five days (and who have not
taken UPA), 7 days of COCP are required before it can be relied on for
contraception (FSRH 2010).

Further research is needed on the effects of quick starting hormonal
contraception after the intake of UPA, so women can be advised regarding the
use of additional non-hormonal contraception.

Currently no interaction data are available about use of ellaOne® with regular
hormonal contraceptives. Because UPA binds the progesterone receptor with high
affinity, it may interfere with the action of progestogen-containing medicinal
products, such as combined hormonal contraceptives. The half-life of UPA is
32.4 hours, and most of the drug is eliminated by 1 week and the interaction
with hormonal contraception is likely to be clinically insignificant by this
time. Starting contraception immediately after EC, rather than waiting for the
next menses, should reduce a woman*s risk of pregnancy.

Primary objective:
To compare the effects of quick starting a combined oral contraceptive on
follicular growth and hormonal parameters after ellaOne® or placebo intake.

Secondary objective:
To compare the effects of quick starting a combined oral contraceptive on
menstrual bleeding patterns and tolerability after ellaOne® or placebo intake.

The study is a multi-center, double-blind, randomized, placebo-controlled trial
in healthy female volunteers.

Participants will receive either ellaOne® or placebo during a spontaneous
cycle, once the dominant follicle is lager than 13 mm. The combined oral
contraceptive will be started the day after and taken once daily for 21 days.

At screening: physical and gynaecological examination including transvaginal
ultrasonography (TVUS).
During treatment: at most of the visits TVUS and venapunction.
Daily diary recording
Urine sampling at home (16 times).
The use of additional non-hormonal contraception.