A prospective, randomized, parallel-group study to assess the effects on ovarian activity of ellaOne (ulipristal acetate 30 mg single dose) taken after three consecutive days of missed combined oral contraceptive pills

INTERVENTION: Trade Name: ellaOne Product Name: ellaOne Pharmaceutical Form: Tablet INN or Proposed INN: ulipristal acetate CAS Number: 126784‐99‐4 Other descriptive name: ULIPRISTAL ACETATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 30‐ Trade Name: Levora Product Name: Levora Pharmaceutical Form: Tablet INN or Proposed INN: LEVONORGESTREL Other descriptive name: levonorgestrel Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.15‐ INN or Proposed INN: ETHINYLESTRADIOL Other descriptive name: ethinylestradiol Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.03‐ CONDITION: Emergency contraception Therapeutic area: Body processes [G] ‐ Metabolic Phenomena [G03] SECONDARY OUTCOME: Secondary end point(s): Safety of treatment intake Timepoint(s) of evaluation of this end point: Analysis of spotting / vaginal bleeding under treatment and occurrence of adverse events. Vital signs and laboratory safety parameters will also be described by quantitative statistics, at each time point INCLUSION CRITERIA: •Women aged 18‐30 years old at screening •Women relying on a COC (containing 30 µg ethinyl estradiol and 7‐day pill‐free (or placebo) interval) as their primary method of contraception for at least 2 cycles before they enter the baseline period and willing to continue with a COC for at least one cycle after end of experimental period •Not at risk of pregnancy: onot sexually active, or owilling to protect all acts of intercourse with condoms, or ohaving undergone surgical sterilization (tubal ligation), or opartner sterilized or vasectomized •BMI < 30.0 kg/m2 •Women able to give informed consent form to participate in the study and willing to comply with all study constraints Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range < PRIMARY OUTCOME: Main Objective: To explore the pharmacodynamic (PD) effects, and specifically on occurrence and timing of ovulation with pregnancy risk, of ellaOne taken after pills of combined oral contraception (COC) were missed for three consecutive days during the first week of COC use and were resumed either on the day of ellaOne intake or five days later. Primary end point(s): a. Ovarian Activity Score (quiescence, ovarian activity, ovulation at risk of pregnancy); b.Occurrence of ovulation with risk of pregnancy; c.Time to ovulation with risk of pregnancy; Secondary Objective: To explore in the 5 days after ellaOne intake the PD effects on ovarian activity (particularly ovulation risk) of ellaOne taken after 3 consecutive COC pills missed in 1st week of use then resumed on ellaOne intake day or 5 days later; To show ovarian activity (particularly occurrence and timing of ovulations) in baseline period (BAS); assess similarity level with experimental period (EXP) where women missed 3 COC pills, took ellaOne, resumed COC on ellaOne intake day or 5 days later; To evaluate ovarian quiescence (OQ) duration &proportion of women with OQ over the 28‐day BAS; To evaluate OQ duration and proportion of women with OQ over the 28‐day EXP where women missed 3 COC pills, took ellaOne, resumed COC on ellaOne intake day or 5 days later; with specific attention to 5 days after ellaOne intake; To evaluate safety (specifically effects on spotting and vaginal bleeding) of ellaOne taken after 3 COC pills missed in 1st week of use then resumed on ellaOne intake day or 5 days later Timepoint(s) of evaluation of this end point: Follicular diameter and levels of hormones in serum will be measured throughout baseline, experimental and post‐experimental periods ; Ovulation at risk of pregnancy will be defined as:; a. A postovulatory image is observed on transvaginal ultrasound. It is defined as follow:; Image observed after abrupt disappearance of FLS OR; Image observed after reduction in size of the leading follicle > 4 mm* at two consecutive visits OR ; Haemorrhagic and cystic corpus luteum (FLS at least as large as the leading follicle before ovulation); b.Estradiol level >0.1 nmol/L; c.Progesterone level >10 nmol/L at two consecutive visits or one level >30 nmol/L;