Effect of Norgestrel 75 mcg Study on Cervical Mucus and Ovarian Activity During Perfect Use, After One Delayed Intake and After a Missed Pill

This study is an exploratory, prospective, multi-center, randomized, cross-over study to
assess the effect of norgestrel 75 mcg on cervical mucus and ovarian activity during reported
perfect daily use, after a delayed intake of 6 hours and after a missed pill.

After a screening period up to one month, depending on the menstrual cycle of the subject,
the subjects will take norgestrel 75 mcg for three 28-day treatment periods, every day at the
same time except for one day in the middle of treatment period 2 and treatment period 3 where
they will either take it 6 hours late or not take it.

They will be randomized to 2 sequences, either 6 hours delayed intake in treatment period 2
and missed pill in treatment period 3 or the opposite.

After the end of treatment period 3, a follow-up up to 12 days may be required to follow
ovarian activities.

Subjects will have visits twice a week and sometimes more often to assess the effects of the
pill on:

- cervical mucus properties by a cervical mucus sampling

- ovarian activity by a vaginal ultrasound (TVUS)

- reproductive hormones levels by a blood sample (Progesterone (P4), Estradiol (E2),
Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH))

- plasma drug level by a blood sample

Inclusion Criteria:

- Women in good overall health with no chronic medical conditions that result in
periodic exacerbations that require significant medical care

- Women between 18 and 35 years inclusive at the screening visit

- BMI< 32 kg/m²

- Regular menstrual cycles between 21 and 35 days when not using hormonal contraception.

- Subjects postpartum or post-abortal must have one normal menstrual cycle (2
menses) prior to enrollment.

- Subjects previously using Intra-Uterine Device (IUD) or taking hormonal
contraception (or any other hormonal treatment, except an injectable treatment)
need to have at least one menstrual cycle (2 menses) without the treatment before
screening.

- Subject previously using an injectable (DMPA), must have had their last injection
at least 9 months before screening.

- Women not at risk of pregnancy: not sexually active, or willing to protect all acts of
intercourse with condoms, or have a sterile partner or have undergone previous tubal
ligation (including validated Essure), or be in a same sex relationship.

- Women able to give informed consent form to participate in the study and in the
opinion of the investigator able to follow all study requirements, use the study
medication and record the requested information appropriately

- Intact uterus and both ovaries

- At least one progesterone concentration > 3 ng/mL (>10 nmol/L) during the luteal phase
of the screening period

Exclusion Criteria:

- Pregnant as confirmed by positive high-sensitivity urine pregnancy test at enrollment
visit

- Trying to conceive or desire to conceive in the next 3 months

- Currently breastfeeding, or within the last 2 months

- Known Polycystic Ovarian Syndrome (PCOS)

- Cancer (or past history of any carcinoma or sarcoma)

- Known abnormal thyroid status, if in clinical judgment of the investigator it cannot
be controlled during the study

- Known hypersensitivity to the ingredients of the test active substances or its
excipients

- Current acute liver disease and/or benign liver tumors

- Have vaginal or cervical infection including clinical evidence of bacterial vaginosis

- Evidence of abnormal cervical lesion

- History of excisional or ablative treatment procedure on cervix (ie. Loop
Electrosurgical Excision Procedure (LEEP), Cryotherapy, Cold Knife Cone)

- Undiagnosed abnormal uterine bleeding

- Prior malabsorptive-type bariatric surgery

- Known or suspected alcoholism or illicit drug abuse

- Use of any hormonal contraception or IUD other than the study medication during the
study (including ulipristal acetate for emergency contraception in the past 5 days)

- Use of any medications that can interfere with the metabolism of progestin-based
contraceptives (e.g CYP3A4 enzymes inducers or inhibitors, etc)

- Unstable diabetes mellitus

- Current participation in any other trial of an investigational medicine or
participation in the past two months (or within 5 elimination half-lives for chemical
entities or 2 elimination half-lives for antibodies, whichever is the longer) before
screening

- Abnormalities in laboratory results or TVUS performed at screening visit recognized as
clinically significant by the investigator

- Conditions not suitable for frequent TVUS examinations, (e.g. virgo intacta)

- In custody or submitted to an institution due to a judicial order

- Relative or household member of the investigator's or sponsor's staff