Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Wome
- Conditions
- Moderate to Severe Vasomotor Symptoms (VMS) in Postmenopausal WomenMedDRA version: 21.0Level: LLTClassification code 10020407Term: Hot flashesSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2019-001289-14-IT
- Lead Sponsor
- Estetra SPR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 1200
1.Signed and dated written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, after the nature of the trial has been explained according to local regulatory requirements;
2.Females, = 40 up to = 65 years of age at randomization/treatment allocation;
3.For hysterectomized subjects: documented hysterectomy must have occurred at least 6 weeks prior to the start of screening. Hysterectomy can be total or subtotal (i.e., cervix was not removed).
4. For non-hysterectomized subjects: uterus with bi-layer endometrial thickness = 4 mm on transvaginal ultrasound (TVUS) (Amendment 1, November 28, 2019);
5.For non-hysterectomized subjects: an evaluable endometrial biopsy taken during screening that reveals no abnormal results, i.e., presence of hyperplasia (simple or complex, with or without atypia), presence of carcinoma, and presence of disordered proliferative findings. The screening biopsy should have sufficient endometrial tissue for diagnosis;
6.Seeking treatment for relief of VMS associated with menopause;
a)For the Efficacy Study part: at least 7 moderate to severe bothersome VMS per day or at least 50 moderate to severe bothersome VMS per week in the last 7 consecutive days during the Screening period ;
b)For the Endometrial and General Safety Study part: at least 1 moderate to severe VMS per week;
7.Body mass index = 18.0 kg/m² to = 38.0 kg/m²;
8.A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening ;
9.Post-menopausal status defined as any of the following:
a)For non-hysterectomized subjects:
-at least 12 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) >40 mIU/ml (value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20);
-or at least 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL and E2 <20 pg/mL (<73.4 pmol/L, value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20) (Amendment 2, February 24, 2020);
-or at least 6 weeks postsurgical bilateral oophorectomy3;
b)For hysterectomized subjects:
-serum FSH >40 mIU/mL and E2 <20 pg/mL (<73.4 pmol/L, values obtained after washout of estrogen/progestin containing drug see exclusion criteria 18 and 20) (Amendment 2, February 24, 2020);
-or at least 6 weeks post-surgical bilateral oophorectomy ;
10.Good physical and mental health, in the judgement of the Investigator as based on medical history, physical and gynecological examination and clinical assessments performed prior to Visit 1;
11.Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions;
12.Able and willing to complete trial daily paper diaries (if applicable, see Section 10.1.7) and questionnaires.
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 1200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin if diagnosed more than 1 year prior to the Screening visit;
2.Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (however, simple cysts confirmed by ultrasound are allowed);
3.PAP test with atypical squamous cells undetermined significance (ASC-US) or higher (low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion [HSIL] [ASC-H], HSIL dysplastic or malignant cells) in sub-totally hysterectomized and non-hysterectomized subjects . Note: ASC-US is allowed if a reflex human papilloma virus (HPV) testing is performed and is negative for high risk oncogene HPV;
4.For non-hysterectomized subjects:
a)History or presence of uterine cancer, endometrial hyperplasia, disordered proliferative findings;
b)Presence of endometrial polyps;
c)Undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding;
d)Endometrial ablation;
e)Any uterine/endometrial abnormality that in the judgment of the investigator contraindicates the use of estrogen and/or progestin therapy. This includes presence or history of adenomyosis or significant myoma (Amendment 2, February 24, 2020);
5.Systolic blood pressure (BP) higher than 130 mmHg, diastolic BP higher than 80 mmHg during screening;
6.History of venous or arterial thromboembolic disease (e.g., superficial or deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, angina pectoris, etc.), or first degree family history of VTE;
7.History of known acquired or congenital coagulopathy or abnormal coagulation factors, including known thrombophilia’s;
8. Laboratory values of fasting glucose ranges above 125 mg/dL (>6.94 mmol/L) and/or glycated hemoglobin above 7% (Amendment 2, February 24, 2020);
9. Dyslipoproteinemia (LDL >190 mg/dL [>4.91 mmol/L] and/or triglycerides >300 mg/dL [>3.39 mmol/L]) (Amendment 1, November 28, 2019 and Amendment 2, February 24, 2020);
10. Subjects smoking >15 cigarettes per day (Amendment 1, November 28, 2019);
11.Presence or history of gallbladder disease, unless cholecystectomy has been performed;
12.Systemic lupus erythematosus;
13.Any malabsorption disorders including gastric bypass surgery;
14.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 [alanine transaminase (ALT) or aspartate transaminase (AST) >2x upper limit of normal (ULN), bilirubin >1.5 ULN]; or liver tumors;
15.Chronic or current acute renal impairment (estimated glomerular filtration rate <60 ml/min);
16.Porphyria;
17.Diagnosis or treatment of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, etc.) in the judgement of the investigator;
Refer to the study protocol for additional exclusion criteria.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method