Minimal Effective Dose of Nomegestrol Acetate Inhibiting the Ovulation in Women Receiving Estradiol

Inclusion criteria

• Female premenopausal healthy volunteers having given their informed written consent at the first selection visit,
• Registered with Social Security in agreement with the French Law on biomedical research on volunteers,
• Sufficiently co-operative to meet the needs of the study,
• Accepting not to become pregnant during the trial,
• Accepting the use of condoms as the single authorized contraceptive means during the trial,
• With a diurnal and regular job or activity,
• Aged 18 to 35 years old inclusive,
• Non-smokers or current smokers of less than 10 cigarettes/day,
• With normal eating habits,
• With a body mass index between 17 and 27 inclusive,

Exclusion criteria

• Participation in another clinical trial,
• Blood donation in the three months prior to Visit V1 or intention to donate blood during the trial or within the three months following the trial completion,
• Virgins, because of the gynecological examination,
• Subjects who were within the exclusion period in the Healthy Volunteers National Register of the French Ministry of Health,
• Forfeiture of freedom by administrative or legal award or under guardianship,
• No possible contact in case of emergency,
• Strenuous physical activity planned during the trial. Concerning the gynecological status and examination
• History of major medical, psychiatric illness or surgery,
• Any acute or chronic systemic disease or disorder,
• History of hypersensitivity to at least one drug (abnormal drug reaction or idiosyncrasy or asthma),
• Abuse of alcohol i.e. history or evidence of acute or chronic abuse, more than 45 g of alcohol per day,
• Excessive drinking of tea, coffee, chocolate, and/or beverages containing caffeine (>5 cups/day or approximately 500 mg of caffeine per day),
• Current vascular pathology or with a past history of thrombo-embolic disease, arterial hypertension (BPS ≥ 160 mm Hg or BPD ≥ 95 mm Hg), coronary artery disease, valvulopathy; thrombogenic cardiac rhythm disturbances, cerebrovascular disease, ocular pathology of vascular origin,
• Cancer or progressive hematological disorder,
• Current or past history of pituitary tumors,
• Epilepsy,
• Known hyperprolactinemia,
• Known renal insufficiency,
• Severe or recent liver disease or symptomatic vesicular lithiasis, or recurrent cholestasis or recurring pruritus of pregnancy,
• Abnormality (> 1N) in liver function on the selection laboratory investigation (ALT or AST > 50 IU/L or alkaline phosphatases > 125 IU/L or total bilirubin > 22 μmol/L or GGT > 70 IU/L),
• Known diabetes or fasting blood sugar > 6.2 mmol/L (1N) at the selection laboratory investigation,
• Uncontrolled treated dyslipidemia or cholesterolemia > 5.2 mmol/L (93%N), then > 6.2 mmol/L (110%N) after protocol amendment during the course of the study, or triglyceridemia > 1.80 mmol/L (79 %N) at the selection laboratory investigation,
• Plasma creatinine > 115 μmol/L (1N),
• Abnormality in any of the hematology parameters,
• Positive results at any of the serologies (HBs antigen, HCV antibodies, HIV 1 & 2 antibodies) performed at V1,
• Positive result for β-HCG at any measurements (i.e. β-HCG > 5 mIU/mL),
• Abnormality in the baseline EKG,
• Connective tissue disorder,
• Porphyria,
• Otosclerosis,
• Abnormality at the medical examination performed at V1 which included a neurological examination,
• Past history or clinical evidence of any malignant tumor or benign disease of the breasts or uterus or ovary (including endometriosis, leiomyomas, polycystic ovaries ...),
• Vaginal infection at the vaginal bacteriological examination performed at V1. After protocol amendment during the course of the study, infection diagnosed at the vaginal bacteriology or at the cervico-vaginal smear was removed from the exclusion criteria list.
• Hysterectomy, even partial, or endometrectomy,
• Pregnancy,
• Childbirth, breast-feeding, miscarriage or termination of pregnancy in the year prior to V1,