Hormonal contraception in woman seeking contraception MedDRA version: 19.0 Level: LLT Classification code 10073728 Term: Hormonal contraception System Organ Class: 100000004865
Conditions
Interventions
Product Name: Estetrol / Drospirenone
Product Code: E4/DRSP
Pharmaceutical Form: Tablet
INN or Proposed INN: Estetrol
CAS Number: 15183-37-6
Current Sponsor code: E4
Other descriptive name: ESTETROL M
Sponsors
Estetra SPRL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy female subjects aged 18-35 years, inclusive, at the time of signing the ICF. 2. Negative pregnancy test at subject screening. 3. Women who ovulate in the Pre-Treatment Cycle between Cycle Day 9 (± 1 day) and Cycle Day 27 (± 1 day) defined as: o TVUS observation of follicle rupture or corpus luteum formation o A subsequent serum progesterone concentration of = 16 nmol/L (when ovulation is observed by TVUS and serum progesterone is close to 16 nmol/L it is at the discretion of the investigator to include a subject), and o Next menstruation does not start within 6 days (± 1 day) after suspected ovulation. 4. Willing to use a non-hormonal method of contraception (e.g. condom) during the wash-out period, Pre-Treatment Cycle and Post-Treatment Cycle. 5. Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, gynecological examination, clinical laboratory, ECG, echocardiography and vital signs. 6. BMI between 18.0 and 35.0 kg/m², inclusive, at time of screening visit. 7. Both ovaries visible by TVUS. 8. Able to fulfill the requirements of the protocol and have indicated a willingness to participate in the study by providing written ICF 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 80 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A menstrual cycle length usually shorter than 21 days or longer than 35 days by history when not using hormonal contraception. 2. No spontaneous menstruation within 46 days after stopping hormonal contraceptive for subjects who need a wash-out cycle. 3. Recent hormone use as follows: a Oral, patch, ring, implant or intra uterine system (IUS) b Injectable 4. Clinically relevant abnormal laboratory result at screening in the opinion of the Principal Investigator (PI) with an understanding of the central laboratory normal range. 5. Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound. 6. Known hypersensitivity to any of the investigational or reference product ingredients. 7. Intention to become pregnant during the course of the study. 8. Pregnancy during accurate hormonal contraceptive use in the past. 9. Currently breastfeeding or before two spontaneous menstruations have occurred after cessation of breastfeeding prior to start of study medication. 10. Less than 6 weeks since last delivery/2nd trimester abortion and before spontaneous menstruation has occurred following a delivery or 2nd trimester abortion. 11. Dyslipoproteinemia requiring active treatment with antilipidemic agent. 12.Diabetes mellitus with vascular involvement or diabetes mellitus of more than 20-year duration. 13. Any arterial hypertension defined by blood pressure values of: a systolic blood pressure = 140 mmHg and/or, b diastolic blood pressure = 90 mmHg. 14. Personal or 1st degree family history of deep vein thrombosis or pulmonary embolism. 15. Current prolonged immobilization or major surgery with prolonged immobilization planned during the study. 16. Known inherited or acquired hypercoagulopathies or thrombogenic mutations. 17. Current treatment with anticoagulants. 18. Presence or history of arterial thromboembolism. 19. Complicated valvular heart disease. 20. History of pregnancy-related cardiomyopathy or moderately or severely impaired cardiac function. 21. Systemic lupus erythematosus. 22. Presence or history of migraine with aura. 23. Within the past 6 months, has had undiagnosed (unexplained) abnormal vaginal bleeding, or any abnormal bleeding that is expected to recur during the trial. 24. Abnormal Papanicolaou (PAP) smear result (PAP score = 2) in the preceding 6 months or a PAP score = 3 at screening. 25. Presence of an undiagnosed breast mass. 26. Current symptomatic gallbladder disease. 27. History of COC related cholestasis. 28. Presence or history of severe hepatic disease as long as liver function values have not returned to normal. 29. Presence or history of pancreatitis if associated with hypertriglyceridemia. 30. Porphyria. 31. Presence or history of hepatocellular adenoma or malignant liver tumors. 32. Renal impairment. 33. Hyperkaliemia or presence of conditions that predispose to hyperkaliemia. 34. History of organ transplantation within 5 years before screening or chronic disease potentially necessitating organ transplantation during the anticipated course of the study. 35. Presence or history of hormone-related malignancy. 36. History of non-hormone-related malignancy within 5 years before screening. Subjects with a non-melanoma skin cancer are allowed in the study. 37. Regular use from screening onwards of drugs potentially triggering interactions with COCs within 12 months prior to screening. 39. Any prior procedure, disease or condition tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effects of the 15 mg E4/3 mg DRSP combination and the 20 mcg EE/3 mg DRSP used as reference combination on ovarian function inhibition at Treatment Cycle 1 and Treatment Cycle 3;Secondary Objective: To evaluate levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone during Treatment Cycle 1, (Treatment Cycle 2), and Treatment Cycle 3. To evaluate endometrial thickness. To evaluate return to fertility. To assess the safety and tolerability of the 15 mg E4/3 mg DRSP and the 20 mcg EE/ 3 mg DRSP combination. To evaluate the effect of 15 mg E4/3 mg DRSP and the 20 mcg EE/3 mg DRSP combination on dysmenorrhea and breast tenderness/pain ;Primary end point(s): Ovarian suppression as assessed with the Hoogland score at Treatment Cycle 1 and Treatment Cycle 3 based on: • follicular size assessed by TVUS • endogenous hormone levels: serum E2, and serum progesterone In case of suspicion of ovulation, additional progesterone measurement will be scheduled on Cycle Day 2, 4 and 6 after suspected ovulation.;Timepoint(s) of evaluation of this end point: Treatment Cycle 1 and Treatment Cycle 3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Levels of serum FSH, LH, E2 and, progesterone Endometrial thickness; Return to fertility Safety and tolerability will be assessed by the monitoring of AEs, vital signs, physical and gynecological examination, clinical laboratory (including the cardiac profile parameters LDH1, LDH2 and troponin I and T), 12-lead ECG and echocardiogram; The effect of 15 mg E4/3 mg DRSP and 20 mcg EE/3 mg DSRP combination on dysmenorrhea and breast tenderness/pain will be assessed using a scoring scale. The scoring scale will ask the subjects to self-assess their perception on dysmenorrhea symptoms and breast tenderness/pain and on a scale of 0 to 10 ranging from no complaints (0) to unbearable complaints (10).;Timepoint(s) of evaluation of this end point: Levels of serum FSH, LH, E2, progesterone and endometrial thickness will be assessed on Cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 (all days ± 1 day) at Treatment Cycle 1 and Treatment Cycle 3 and on Cycle Day 3 (± 1 day) of Treatment Cycle 2; Return to fertility will be assessed every 3 days from Cycle Day 3 of the Post-Treatment Cycle until ovulation occurs or until Cycle Day 36. Ovulation will be confirmed by measurement of serum progesterone 2 days after the suspected ovulation. If serum progesterone is < 16 nmol/L, a second measurement of serum progesterone will be obtained 4 days after the suspected ovulation; Safety and tolerability, dysmenorrhea and breast tenderness/pain will be assessed throughout the study | — |
Countries
Netherlands
Contacts
Public ContactClinical Study Leader
Estetra SPRL
Outcome results
None listed