A Study to Evaluate Estetrol to Treat Moderate-to-Severe Vasomotor Symptoms in Postmenopausal Women

Overview

About this study

The purpose of this two-part study is to evaluate the effect of 15 or 20 mg of Estetrol (E4), or placebo, on the severity and frequency of vasomotor symptoms (VMS) (Efficacy Study Part) and the safety of E4 20 mg (Safety Study Part) in postmenopausal women.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 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 (Amendment 3, 08 October 2019 and Amendment 4, 03 February 2020).
  • For non-hysterectomized subjects: 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. Biopsies without tissue or with insufficient tissue may be repeated once.
  • 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 Safety Study part: at least 1 moderate to severe VMS per week.
  • Body mass index ≥ 18.0 kg/m² to ≤ 38.0 kg/m².
  • 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:
    • or at least 6 weeks postsurgical bilateral oophorectomy;
    • or at least 6 months of spontaneous amenorrhea with serum FSH > 40 mIU /mL and E2 < 20 pg/mL (value obtained after washout of estrogen/progestin containing drugs;
    • or at least 6 weeks postsurgical bilateral oophorectomy.
  • For hysterectomized subjects:
    • serum FSH > 40 mIU/mL and E2 < 20 pg/mL (values obtained after washout of estrogen/progestin containing drug;
    • 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 to Visit 1.
  • Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions.
  • Able and willing to complete trial daily diaries and questionnaires.

* Subjects must have a Breast Imaging-Reporting And Data System (BI-RADS) score of 1 or 2 to enroll in the study. An incomplete mammogram result, i.e., BI-RADS 0, is not acceptable. and requires further assessment (Amendment 5, 23 September, 2020). The site must obtain a copy of the official report for the subject's study file. A digitalized imaging should be obtained if mammography is done as part of this study.

Exclusion Criteria:

  • 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 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.
  • For non-hysterectomized subjects:
    • History or presence of uterine cancer, endometrial hyperplasia, disordered proliferative findings;
    • Presence of endometrial polyp;
    • Undiagnosed vaginal bleeding;
    • Endometrial ablation;
    • Enlarged uterus with 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 of congenital coagulopathy or abnormal coagulation factors, including known thrombophilias.
  • Diabetes mellitus with poor glycemic control in the last 6 months assessed by laboratory values of fasting glucose outside the normal ranges and glycated hemoglobin above 7%.
  • Dyslipoproteinaemia (LDL > 190 mg/dL and triglycerides > 300 mg/dL).
  • Smoking:
    • Efficacy Study part: subjects smoking > 5 cigarettes per day or > 2 packs per week;
    • Safety Study part: subjects smoking > 15 cigarettes per day or > 6 packs per week.
  • 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 of chronic liver disease [alanine transaminase (ALT) or aspartate transaminase (AST) >2 x upper limit of normal (ULN), bilirubin >1.5 ULN].
  • 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.
    • 8 weeks before screening start for oral estrogen and/or progestin products and/or selective estrogen receptor modulator therapy.
    • 8 weeks before screening start for intrauterine progestin therapy.
    • 3 months before screening start for progestin implants or estrogen alone injectable drug therapy.
    • 6 months before screening start for estrogen pellet therapy or progestin injectable drug therapy.
    • Use of androgen/ dehydroepiandrosterone (DHEA) containing drugs:
      • 8 weeks before screening start for oral, topical, vaginal or transdermal androgen;
      • 6 months before screening start for implantable or injectable androgen therapy.
  • Use of phytoestrogens or black cohosh for treatment of VMS up to 2 weeks before the start of screening.
  • For the women participating in the Efficacy Study part: use of prescription or over-the-counter products used for the treatment of VMS; e.g., anti-depressants: paroxetine, escitalopram, methyldopa, opioid and clonidine up to 4 weeks before the start of screening, and venlafaxine and desvenlafaxine up to 3 months before the start of screening , and not willing to stop these during their participation in the trial.
  • Inadequately treated hyperthyroidism at screening.
  • History or presence of allergy/intolerance to the investigational product 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.
  • For non-hysterectomized subjects: history or presence of allergy to peanuts.
  • 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.
  • Sponsor or contract research organization (CRO) employees or employees under the direct supervision of the Investigator and/or involved directly in the trial.
  • 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 risk to the subject in the opinion of the Investigator.
  • Participation in another investigational drug clinical trial within 1 month (30 days) or having received an investigational drug within the last 1 month (30 days) before the start of screening.
  • Is judged by the Investigator to be unsuitable for any reason.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ekta Kapoor, M.B.B.S.

Open for enrollment

Contact information:

Shawn Fokken CCRP

(507) 293-2740

GIMRESEARCHSTUDIES@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20486869

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