A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms

Completed · Phase 3 · Has a placebo group

Conditions studied: Menopause

In brief

This study will be a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial of postmenopausal subjects with an intact uterus.

Key facts

Study ID

NCT01942668

Run by

TherapeuticsMD

People needed

1845

Starts

2013-08-05

Expected to finish

2016-10-28

Last updated by the study team

2019-05-06

Who can join

Age: 40 and older, up to 65. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Be a female between the ages of 40 and 65 years (at the time of randomization) who is willing to participate in the study, as documented by signing the informed consent form.
• Be a postmenopausal woman with an intact uterus and a Screening serum estradiol level of ≤50 pg/mL. Postmenopausal is defined herein as:
• ≥ 12 months of spontaneous amenorrhea, or
• at least 6 months of spontaneous amenorrhea with a Screening serum FSH level of >40 mIU/ml, or
• ≥ 6 weeks postsurgical bilateral oophorectomy.
• Be seeking treatment or relief for vasomotor symptoms associated with menopause.
• To participate in the VMS Substudy, a subject must also report ≥7 moderate to severe hot flushes per day, or ≥50 per week, at the baseline assessment during Screening (subjects whose hot flushes are less frequent may still participate as non-Substudy subjects.
• Note: A minimum of 14 consecutive days of complete hot flush diary data are required during the baseline assessment at Screening, and these consecutive days must occur within the last 14 days prior to the Randomization visit (not counting the Randomization visit day itself). The most recent 7 consecutive days of data prior to randomization (Day -7 to Day -1) will be used to determine the baseline number of mild, moderate and severe hot flushes for each subject.
• Have a Body Mass Index (BMI) less than or equal to 34 kg/mP2P. (BMI values should be rounded to the nearest integer [e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27]).
• Be willing to abstain from using products (other than study medication) that contain estrogen, progestin, or progesterone throughout study participation.
• Be judged by the principal or sub-investigator physician as being in otherwise generally good health based on a medical evaluation performed during the Screening period prior to the initial dose of study medication. The medical evaluation findings must include:
• a normal or non-clinically significant physical examination, including vital signs (sitting blood pressure, heart rate, respiratory rate and temperature). Sitting systolic blood pressure is ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications.
• a normal or non-clinically significant pelvic examination.
• a mammogram that shows no sign of significant disease (can be performed within previous 6 months prior to initial dose of study medication). Subjects must have a BI-RADS 1 or 2 to enroll in the study. An incomplete mammogram result, i.e. BI-RADS 0, is not acceptable. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment.
• a normal or non-clinically significant clinical breast examination. An acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
• a normal Screening Papanicolaou ("Pap") smear. (Subjects with findings of atypical glandular cells [AGC], AGUS, ASCUS with high risk HPV type upon reflex testing, LSIL, ASC-H, HSIL, dysplastic cells, or malignant cells must be excluded from randomization.)
• an acceptable result from an evaluable Screening endometrial biopsy. The endometrial biopsy reports by the two central pathologists at Screening must each specify one of the following: proliferative endometrium; weakly proliferative endometrium; disordered proliferative pattern; secretory endometrium; endometrial tissue other (including benign, inactive or atrophic fragments of endometrial epithelium, glands, stroma, etc); endometrial tissue insufficient for diagnosis; no endometrium identified; or no tissue identified. However, at least one pathologist must identify sufficient tissue to evaluate the biopsy. Additionally, the endometrial biopsy reports by the two central pathologists of Other Findings at Screening must each specify one of the following: endometrial polyp not present; benign endometrial polyp; or polyp other. (See Exclusion criterion #27)
• a normal or non-clinically significant 12-lead ECG.

You may not qualify if…

• To participate in the study, a subject must NOT:
• Be currently hospitalized.
• Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder.
• Have a history of coronary artery or cerebrovascular disease (e.g., myocardial infarction, angina, stroke, TIA).
• Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure).
• Have a history of a malabsorption disorder (e.g., gastric bypass, Crohn's disease).
• Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed.
• Have a history of diabetes, thyroid disease or any other endocrinological disease. (Subjects with diet-controlled diabetes or controlled hypothyroid disease at Screening are not excluded.)
• Have a history of estrogen-dependent neoplasia.
• Have a history of atypical ductal hyperplasia of the breast.
• Have a finding of clinically significant uterine fibroids at Screening.
• Have had a uterine ablation.
• Have a history of undiagnosed vaginal bleeding.
• Have any history of endometrial hyperplasia, melanoma, or uterine/endometrial, breast or ovarian cancer.
• Have any history of other malignancy within the last 5 years, with the exception of basal cell (excluded if within 1 year) or non-invasive squamous cell (excluded if within 1 year) carcinoma of the skin.
• Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological (e.g., bipolar disorder, schizophrenia, major depressive disorder), or musculoskeletal disease or disorder that is clinically significant in the opinion of the Principal Investigator or Medical Sub-Investigator.
• Have any of the following clinical laboratory values at Screening:
• fasting triglyceride of ≥300 mg/dL and/or total cholesterol of ≥300mg/dL
• positive laboratory finding for Factor V Leiden mutation
• AST or ALT ≥1.5 times the upper limit of normal (ULN)
• fasting glucose >125 mg/dL
• Be known to be pregnant or have a positive urine pregnancy test. (Note: A pregnancy test is not required for subjects who have had bilateral tubal ligation, bilateral oophorectomy, or are 55 years old or greater and have experienced cessation of menses for at least 1 year.)
• Have contraindication to estrogen and/or progestin therapy or allergy to the use of estradiol and/or progesterone or any components of the investigational drugs.
• Use 15 or more cigarettes per day or currently use any electronic cigarettes.
• Have a history of drug and/or alcohol abuse within one year of start of study.

Where it is running

• Medical Affiliated Research Center — Huntsville, Alabama, United States
• Coastal Clinical Research — Mobile, Alabama, United States
• Mobile Ob-Gyn, P.C. — Mobile, Alabama, United States
• Montgomery Women's Health — Montgomery, Alabama, United States
• Advanced Research Associates — Glendale, Arizona, United States
• Cactus Clinical Research — Mesa, Arizona, United States
• Precision Trials — Phoenix, Arizona, United States
• Radiant Research (Tucson) — Tucson, Arizona, United States
• Visions Clinical Research Tucson — Tucson, Arizona, United States
• Health Star Research, LLC — Hot Springs, Arkansas, United States
• Sutter East Bay Medical Foundation — Berkeley, California, United States
• Grossmont Center for Clinical Research — La Mesa, California, United States
• Futura Research — Norwalk, California, United States
• Medical Center for Clinical Research — San Diego, California, United States
• Women's Health Care Research Corp. — San Diego, California, United States
• Radiant Research, Inc. — Santa Rosa, California, United States
• Diablo Clinical Research — Walnut Creek, California, United States
• Downtown Women's Healthcare — Denver, Colorado, United States
• Horizon's Clinical Research Center — Denver, Colorado, United States
• Red Rocks OB/Gyn — Lakewood, Colorado, United States
• Clinical Research Consulting — Milford, Connecticut, United States
• Coastal Connecticut Research — New London, Connecticut, United States
• South Florida Medical Research — Aventura, Florida, United States
• Nature Coast Clinical Research — Crystal River, Florida, United States
• Simon Williamson Clinic — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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