Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort Study I)

Completed · Phase 3 · Has a placebo group

Conditions studied: Vasomotor Symptoms, Menopausal Symptoms

In brief

This is a two-part study designed to evaluate the effect of Estetrol (E4) 15 or 20 mg, or placebo on the severity and frequency of vasomotor symptoms (VMS) (Efficacy Study Part) and the safety of E4 20 mg (Endometrial and General Safety Study Part)

Key facts

Study ID

NCT04209543

Run by

Estetra

People needed

1570

Starts

2019-12-30

Expected to finish

2024-02-08

Last updated by the study team

2025-01-29

Who can join

Age: 40 and older, up to 65. Sex: female. Healthy volunteers: accepted.

You may qualify if…

• 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;
• Females, ≥ 40 up to ≤ 65 years of age at randomization;
• 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);
• For non-hysterectomized subjects: uterus with bi-layer endometrial thickness ≤ 4 mm on TVUS;
• 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 endometrium findings. The screening biopsy should have sufficient endometrial tissue for diagnosis;
• Seeking treatment for relief of VMS associated with menopause;
• 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;
• For the Endometrial and General Safety Study part: at least 1 moderate to severe VMS per week;
• Body mass index ≥ 18.0 kg/m\^2 to ≤ 38.0 kg/m\^2;
• A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening ;
• Post-menopausal status defined as any of the following:
• For non-hysterectomized subjects:
• at least 12 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) >40 milli-International unit (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);
• or at least 6 weeks postsurgical bilateral oophorectomy;
• 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);
• or at least 6 weeks post-surgical bilateral oophorectomy.
• 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 Visit 1;
• Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions;
• Able and willing to complete trial daily paper diaries (if applicable) and questionnaires.

You may not qualify if…

• 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;
• 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);
• Papanicolaou (PAP) test with atypical squamous cells undetermined significance (ASC-US) or higher (low-grade intraepithelial lesion [LSIL], atypical squamous cells- cannot exclude high-grade 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 subtypes 16 and 18;
• For non-hysterectomized subjects:
• History or presence of uterine cancer, endometrial hyperplasia, or disordered proliferative endometrium;
• Presence of endometrial polyps;
• Undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding;
• Endometrial ablation;
• 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;
• Systolic blood pressure (BP) higher than 130 mmHg, diastolic BP higher than 80 mmHg during screening;
• 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 venous thromboembolism (VTE);
• History of known acquired or congenital coagulopathy or abnormal coagulation factors, including known thrombophilia's;
• Laboratory values of fasting glucose above 125 mg/dL (>6.94 mmol/L) and/or glycated hemoglobin above 7%18;
• Dyslipoproteinemia (LDL >190 mg/dL [>4.91 mmol/L] and/or triglycerides >300 mg/dL [>3.39 mmol/L])19;
• Subjects smoking >15 cigarettes per day;
• Presence or history of gallbladder disease, unless cholecystectomy has been performed;
• Systemic lupus erythematosus;
• Any malabsorption disorders including gastric by-pass surgery;
• 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;
• Chronic or current acute renal impairment (estimated glomerular filtration rate <60 ml/min);
• Porphyria;
• Diagnosis or treatment of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, etc.), in the judgement of the Investigator;
• Use of estrogen/progestin containing drug(s) up to:
• 1 week before screening start for vaginal non systemic hormonal products (rings, creams, gels);
• 4 weeks before screening start for vaginal or transdermal estrogen or estrogen/progestin products;

Where it is running

• Estetra Study Site — Mesa, Arizona, United States
• Estetra Study Site — Phoenix, Arizona, United States
• Precision Trials AZ, LLC — Phoenix, Arizona, United States
• Noble Clinical Research — Tucson, Arizona, United States
• Hope Clinical Research, LLC — Canoga Park, California, United States
• Estetra Study Site — Pomona, California, United States
• Clinical Trials Research — Sacramento, California, United States
• Estetra Study Site — Sacramento, California, United States
• Estetra Study Site — Thousand Oaks, California, United States
• Estetra Study Site — West Covina, California, United States
• Velocity Clinical Research — Denver, Colorado, United States
• Estetra Study Site — Altamonte Springs, Florida, United States
• Estetra Study Site — Coconut Creek, Florida, United States
• Estetra Study Site — Hialeah, Florida, United States
• Clinical Neuroscience Solutions, Inc. — Jacksonville, Florida, United States
• Altus Research — Lake Worth, Florida, United States
• Medical Research Center of Miami II — Miami, Florida, United States
• Miami Clinical Research — Miami, Florida, United States
• Genoma Research Group, Inc. — Miami, Florida, United States
• Estetra Study Site — Miami, Florida, United States
• San Marcus Research Clinic, Inc. — Miami Lakes, Florida, United States
• Estetra Study Site — New Port Richey, Florida, United States
• Estetra Study Site — North Miami, Florida, United States
• Estetra Study Site — Ocoee, Florida, United States
• Estetra Study Site — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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