postmenopausal women with vasomotor menopausal symptoms
Conditions
Interventions
Product Name: Estetrol (E4) 20 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Estetrol monohydrate (E4)
CAS Number: 2055649-81-3
Current Sponsor code: E4
Other descriptive name: Este
Sponsors
Estetra Srl
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written IC form and any required privacy authorization prior to the initiation of any study procedure, after the nature of the study has been explained according to local regulatory requirements 2. Females, =40 to =65 years of age (inclusive) at randomization/treatment allocation visit with vasomotor menopausal symptoms. 3. Postmenopausal status defined as any of the following: a. For NH subjects: ? At least 12 months of spontaneous amenorrhea with serum FSH >40 mIU/mL and E2 40 mIU/mL and E2 =65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. History of malignancy 2. Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy 3. Abnormal cervical cytology on PAP smear within the prior year 4. For NH subjects: Presence of uterine cancer, endometrial hyperplasia, disordered proliferative or endometriumendometrial polyp(s); undiagnosed vaginal bleeding or abnormal uterine bleeding 5. Systolic BP higher than 139 mmHg, diastolic BP higher than 89 mmHg 6. History of venous or arterial thromboembolic disease or first-degree family history of VTE 7. History of known acquired of congenital coagulopathy or abnormal coagulation factors (incl. known thrombophilia) 8. Laboratory values of glycated hemoglobin above 7.5% 9. Are current smokers (non-smokers of at least one year) 10. Presence or history of gallbladder disease unless cholecystectomy has been performed 11. Systemic lupus erythematosus 12. Any malabsorption disorders including gastric bypass surgery 13. History of acute liver disease in the preceding 12 months before the start of screening or presence or history of chronic or severe liver disease or liver tumors 14. Chronic or current acute renal impairment 15. Inadequately treated hyperthyroidism with abnormal thyroid stimulating hormone and free thyroxine at screening 16. Porphyria 17. Diagnosis or treatment of major psychiatric disorder in the judgement of the Investigator 18. Use of estrogen/progestina up to: a.1 week before screening start for vaginal non-systemic hormonal products (rings, creams, gels); b. 4 weeks before screening start for vaginal or transdermal estrogen or estrogen/progestin products; c. 8 weeks before screening start for oral estrogen and/or progestin products and/or selective estrogen receptor modulator therapy; d. 8 weeks before screening start for intrauterine progestin therapy; e. 3 months before screening start for progestin implants or estrogen alone injectable drug therapy; f. 6 months before screening start for estrogen pellet therapy or progestin injectable drug therapy 19. Use of androgen/dehydroepiandrosterone containing drugs: a. 8 weeks before screening start for oral, topical, vaginal, or transdermal androgen; b. 6 months before screening start for implantable or injectable androgen therapy 20. Use of phytoestrogens or black cohosh for treatment of VMS up to 2 weeks before the start of screening 21. Not willing to stop any hormonal products as described in exclusion criteria 18, 19 and 20, during their participation in the study 22. History or presence of allergy/intolerance to the IMP or drugs of this class or any component of it, or history of drug or other allergy that, in the opinion of the Investigator contraindicates subject participation 23. For NH subjects: history or presence of allergy to progestogens 24. History of alcohol or substance abuse (including marijuana, even if legally allowed) or dependence in the previous 12 months before the start of screening as determined by the Investigator, based on reported observations 25. Sponsor or CRO employees or employees under the direct supervision of the Investigator and/or involved directly in the study or close affiliation with the investigator (e.g., a close relative) or persons working at the CRO or at the site 26. Subjects with known or suspected history of a clinically significant systemic disease, unstable medical disorders, life-threatening disease, or current malignancies that would pose a r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy: • assess the influence of treatment with E4 20 mg compared with placebo on skin parameters by measurement of skin elasticity and roughness Safety: • evaluate the general safety of treatment with E4 20 mg compared with placebo • evaluate the effect of treatment with E4 20 mg on the endometrium in non-hysterectomized (NH) subjects compared with placebo • evaluate the frequency (number of days) of vaginal bleeding in NH subjects treated with E4 20 mg compared with placebo;Secondary Objective: Efficacy: • Analysis of collagen content (quantitative) • Skin hydration • Thickness of the dermis • Skin thickness • Fine wrinkles and volume • Skin status including dryness • Quality of life (QoL, using the Dermatology Life Quality Index [DLQI]);Primary end point(s): Efficacy endpoints: (dermatological efficacy endpoints; mean changes from baseline (dermatological screening visit) to Week 22) • Skin elasticity (R0 [mm], R2 [ratio] and R7 [ratio]) as measured by cutometry. • Roughness (Ra, Rmax, and Rzm) [µm] as measured by phaseshift rapid in vivo measurement of skin (PRIMOS) CR-System from photos taken from the face. Safety endpoints: • Frequency of TEAEs (including treatment emergent SAEs). • Frequency of changes in results in physical and gynecological examination, vital signs, and breast examination at each measured time point. • Frequency of changes in routine clinical laboratory tests results (hematology and chemistry) at each measured time point. • Change from baseline (screening visit) to each measured time point in endometrial thickness measured by ultrasound. • Proportion of women with vaginal bleeding and/or spotting during each 28-day cycle of treatment with E4 based on recording in the subject diary (for NH subjects only). • Proportion of women with amenorrhea (absence of any bleeding or spotting) during each 28-day cycle of treatment with E4 based on recording in the subject diary (for NH subjects only).;Timepoint(s) of evaluation of th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: (mean changes from baseline (dermatological screening visit) to week 22) • Collagen content [2 -??Ct] analyzed in skin biopsies from upper arm or forearm (inner side) (same location as for sonography measurement). • Skin hydration [arbitrary units (a.u.)] as measured by corneometry. • Thickness of dermis [µm] measured in skin biopsies from upper arm or forearm (inner side). • Skin thickness [µm] measured by sonography on upper arm or forearm (inner side). • Fine wrinkles and volume (wrinkle fractional area [%change], total wrinkle length [mm], wrinkle surface area [mm²], wrinkle volume [mm³], max wrinkle depth [µm]) analyzed by PRIMOS CR-System from photos taken from the face. • Skin dryness assessed by investigator using a 5-point scale (from 0 = none to 4 = severe).1 • QoL assessed by DLQI.;Timepoint(s) of evaluation of this end point: Week 22 | — |
Countries
Germany
Contacts
Public ContactSigrid Schollen
Estetra Srl
Outcome results
None listed