Study: Therapeutics-MD - TXC12-05
Diablo Clinical Research
2255 Ygnacio Valley Road, Suite M
Walnut Creek, CA 94598
This study will be a prospective, randomized, double-blind, placebo-controlled trial of postmenopausal subjects with an intact uterus. To reduce the frequency and severity of hot flashes in postmenopausal women.
A Phase 3 Study Safety and Efficacy Study of the Combination of Estradiol and Progesterone to Treat Hot Flash Symptoms in Postmenopausal Women With an Intact Uterus.
Qualifications - Inclusions & Exclusions:
- 1. 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.2. Be a postmenopausal woman with an intact uterus and at least 6 months of spontaneous amenorrhea, with a Screening serum FSH level of >40 mIU/ml and a Screening serum estradiol level of ≤50 pg/mL.3. 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. The most recent 7 consecutive days of data prior to randomization will be used to determine the baseline number of mild, moderate and severe hot flushes for each subject. The number of moderate to severe hot flushes from these 7 days will also be used to determine eligibility for the VMS Substudy.
4. 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]).
5. Be willing to abstain from using products (other than study medication) that contain estrogen, progestin, or progesterone throughout study participation.
6. Be judged by the principal or sub-investigator physician as being in otherwise generally good health based on a pre-study medical evaluation performed within 42 days 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).
- 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). An acceptable mammogram is defined as a mammogram in which no masses or other findings are identified that is suspicious of malignancy. 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.
- a normal or non-clinically significant 12-lead ECG.
- sitting systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications.
- 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.
- Have a history of liver or kidney dysfunction/disorder.
- Have a history of a malabsorption disorder.
- 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 a history of undiagnosed vaginal bleeding.
- Have any history of endometrial hyperplasia 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, 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:
- 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)
- hemoglobin ≤10 g/dL or >15.5 g/dL or Hematocrit >51%
- platelet count ≤150,000/mmP3P or ≥450,000/mmP3
- total bilirubin ≥1.5 times ULN
- creatinine ≥1.2 mg/dL
- fasting glucose >125 mg/dL
- alkaline phosphatase ≥1.5 times ULN
- 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.
- Have a history of drug and/or alcohol abuse within one year of start of study.
- Have used, within 28 days prior to the initial dose of study medication at Visit 1, any medication known to induce or inhibit CYP3A4 enzyme activity that may affect estrogen and/or progestin drug metabolism. (See Prohibited Medications, 48TUSection 4.4U48T)
- Have used, within 28 days prior to Screening, or plan to use during the study, any prescription or over-the-counter (OTC) medications (including herbal products, such as St. John’s Wort) that would be expected to alter progesterone or estrogen activity. (See Prohibited Medications, 48TUSection 4.4U48T)
- Have used estrogen alone or estrogen/progestin, testosterone, or estrogen/testosterone for any of the following time periods:
- Vaginal hormonal products (rings, creams, gels) within 7 days prior to Screening.
- Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening.
- Oral estrogen and/or progestin therapy within 8 weeks prior to Screening.
- Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening.
- Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening.
- Percutaneous estrogen lotions/gels within 8 weeks prior to Screening.
- Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening.
- Have used an intrauterine device (IUD) within the 12 weeks prior to Screening.
- Have any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study or complying with protocol requirements.
- Have a Screening endometrial biopsy sample that is found by both primary pathologists to have endometrial tissue insufficient for diagnosis, no endometrium identified, or no tissue identified. (With the approval of the Medical Monitor, the screening endometrial biopsy may be repeated once.)
- Have contraindication to any planned study assessments (e.g., endometrial biopsy).
Compensation for Time and Travel:
Our patient volunteers receive all labs, physical exams, study medication free of charge. No insurance is required. Volunteers may be compensated for time and travel.