Clinical trial NCT01942668: A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms
Official title: A Phase 3 Study Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms in Postmenopausal Women With an Intact Uterus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Menopause
Keywords: Vasomotor symptoms
Hot flashes
Endometrial protection
Lead sponsor: TherapeuticsMD
Sponsor class: INDUSTRY
First posted: 2013-09-16
Enrollment: 1845
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: Postmenopausal subjects with an intact uterus who meet the study entry criteria will be randomized to one of five treatment arms (four active and one placebo) and followed for 12 months. During the Screening period all subjects will be provided with a diary to self-assess the frequency and severity of their vasomotor symptoms. Subjects experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will participate in a VMS Substudy during the first 12 weeks of treatment. The Substudy subjects will be stratified by treatment arm within the sites, and only Substudy subjects have the possibility of being randomized to placebo. Subjects who qualify for the study except for experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will be stratified within sites to one of the four active treatment arms and followed for 12 months, but will not participate in the VMS Substudy. (However, VMS information will be collected from all subjects during the first 12 weeks of treatment.) All Study Subjects: Postmenopausal women with an intact uterus who seek relief from hot flushes and meet all other inclusion/exclusion criteria are eligible for 12 months of study treatment.

VMS Substudy Subjects: A subset of All Study Subjects who have ≥7 per day or ≥50 per week moderate to severe hot flushes (as determined during Screening) are eligible for the 12-week VMS Substudy and for a total of 12 months of study treatment.

Clinical evaluations will be performed at the following time points:

* Screening Period (Week: - 8.5) (up to -60 Days)
* Visit 1 Randomization (Week 0) (Day 1)
* Visit 2 Interim (Week 4)
* Visit 3 Interim (Week 8)
* Visit 4 Interim (Week 12)
* Visit 5 Interim (Month 6)
* Visit 6 Interim (Month 9)
* Visit 7 End of Treatment (Month 12)

Eligibility criteria: Inclusion Criteria:

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 a Screening serum estradiol level of ≤50 pg/mL. Postmenopausal is defined herein as:

   1. ≥ 12 months of spontaneous amenorrhea, or
   2. at least 6 months of spontaneous amenorrhea with a Screening serum FSH level of \>40 mIU/ml, or
   3. ≥ 6 weeks postsurgical bilateral oophorectomy.
3. Be seeking treatment or relief for vasomotor symptoms associated with menopause.
4. 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.
5. Have a Body Mass Index (BMI) less than or equal to 34 kg/mP2P. (BMI values should be rounded to the nearest integer \[e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27\]).
6. Be willing to abstain from using products (other than study medication) that contain estrogen, progestin, or progesterone throughout study participation.
7. 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:

   1. 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.
   2. a normal or non-clinically significant pelvic examination.
   3. 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.
   4. 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.
   5. 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.)
   6. 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)
   7. a normal or non-clinically significant 12-lead ECG.

Exclusion Criteria:

* To participate in the study, a subject must NOT:

  1. Be currently hospitalized.
  2. Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder.
  3. Have a history of coronary artery or cerebrovascular disease (e.g., myocardial infarction, angina, stroke, TIA).
  4. Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure).
  5. Have a history of a malabsorption disorder (e.g., gastric bypass, Crohn's disease).
  6. Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed.
  7. 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.)
  8. Have a history of estrogen-dependent neoplasia.
  9. Have a history of atypical ductal hyperplasia of the breast.
  10. Have a finding of clinically significant uterine fibroids at Screening.
  11. Have had a uterine ablation.
  12. Have a history of undiagnosed vaginal bleeding.
  13. Have any history of endometrial hyperplasia, melanoma, or uterine/endometrial, breast or ovarian cancer.
  14. 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.
  15. 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.
  16. Have any of the following clinical laboratory values at Screening:

      1. fasting triglyceride of ≥300 mg/dL and/or total cholesterol of ≥300mg/dL
      2. positive laboratory finding for Factor V Leiden mutation
      3. AST or ALT ≥1.5 times the upper limit of normal (ULN)
      4. fasting glucose \>125 mg/dL
  17. 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.)
  18. 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.
  19. Use 15 or more cigarettes per day or currently use any electronic cigarettes.
  20. Have a history of drug and/or alcohol abuse within one year of start of study.
  21. 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 48TUSection 4.3U48T)
  22. 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 or is being used to treat vasomotor symptoms. (See Section 4.3U48T)
  23. Have used estrogen alone or estrogen/progestin, SERM (selective estrogen receptor modulator), testosterone, or estrogen/testosterone for any of the following time periods:

      1. Vaginal nonsystemic hormonal products (rings, creams, gels) within 7 days prior to Screening, or vaginal systemic products (e.g., FemRing) within 28 days prior to Screening.
      2. Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening.
      3. Oral estrogen and/or progestin and/or SERM therapy within 8 weeks prior to Screening.
      4. Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening.
      5. Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening.
      6. Percutaneous estrogen lotions/gels within 8 weeks prior to Screening.
      7. Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening.
  24. Have used an intrauterine device (IUD) within the 12 weeks prior to Screening.
  25. For subjects in the VMS Substudy only: use of medication that may affect the outcome of the vasomotor symptom endpoints within 28 days prior to Screening (e.g. SSRIs \[selective serotonin reuptake inhibitors\], SNRIs \[serotonin and norepinephrine reuptake inhibitors\], aldomet, dopaminergic or antidopaminergic drugs, gabapentin, clonidine, or bellergal.)
  26. 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.
  27. 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.)
  28. Endometrial polyps with atypical nuclei reported by at least 1 central pathologist.
  29. Have contraindication to any planned study assessments (e.g., endometrial biopsy).
  30. Have participated in another clinical trial within 30 days prior to Screening, have received an investigational drug within the three months prior to the initial dose of study medication, or be likely to participate in a clinical trial or receive another investigational medication during the study.
  31. Currently use marijuana.

Primary outcomes:
measure: Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Primary Safety Endpoint: Endometrial Protection - Hyperplasia
timeFrame: Baseline and Month 12
Secondary outcomes:
measure: Endometrial Protection - Hyperplasia
timeFrame: Baseline and Month 12
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Severity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)
timeFrame: Baseline and Week 1
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)
timeFrame: Baseline and Week 2
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)
timeFrame: Baseline and Week 3
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)
timeFrame: Baseline and Week 5
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)
timeFrame: Baseline and Week 6
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)
timeFrame: Baseline and Week 7
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)
timeFrame: Baseline and Week 9
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)
timeFrame: Baseline and Week 10
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)
timeFrame: Baseline and Week 11
measure: Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Clinical Global Impression (CGI) - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)
timeFrame: Baseline and Week 4
measure: Clinical Global Impression (CGI) - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)
timeFrame: Baseline and Week 8
measure: Clinical Global Impression (CGI) - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 1 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 2 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 3 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 4 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 5 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 6 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 7 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 8 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 9 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 10 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 11 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: Cycle 12 to 13
measure: Number of Subjects Without Bleeding for Consecutive Cycles
timeFrame: The 13th Cycle
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 1 to 13
timeFrame: Cycle 1 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 2 to 13
timeFrame: Cycle 2 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 3 to 13
timeFrame: Cycle 3 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 4 to 13
timeFrame: Cycle 4 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 5 to 13
timeFrame: Cycle 5 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 6 to 13
timeFrame: Cycle 6 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 7 to 13
timeFrame: Cycle 7 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 8 to 13
timeFrame: Cycle 8 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 9 to 13
timeFrame: Cycle 9 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 10 to 13
timeFrame: Cycle 10 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 11 to 13
timeFrame: Cycle 11 to 13
measure: Number of Subjects With Cumulative Amenorrhea From Cycle 12 to 13
timeFrame: Cycle 12 to 13
measure: Number of Subjects With Cumulative Amenorrhea From the 13th Cycle
timeFrame: The 13th Cycle
measure: Subject Incidence With Spotting - Trimester 1 (Safety Pop.)
timeFrame: Trimester 1
measure: Subject Incidence With Spotting - Trimester 2 (Safety Pop.)
timeFrame: Trimester 2
measure: Subject Incidence With Spotting - Trimester 3 (Safety Pop.)
timeFrame: Trimester 3
measure: Subject Incidence With Spotting - Trimester 4 (Safety Pop.)
timeFrame: Trimester 4
measure: Number of Days With Spotting - Trimester 1 (Safety Pop.)
timeFrame: Trimester 1
measure: Number of Days With Spotting - Trimester 2 (Safety Pop.)
timeFrame: Trimester 2
measure: Number of Days With Spotting - Trimester 3 (Safety Pop.)
timeFrame: Trimester 3
measure: Number of Days With Spotting - Trimester 4 (Safety Pop.)
timeFrame: Trimester 4
measure: Subject Incidence With Bleeding - Trimester 1 (Safety Pop.)
timeFrame: Trimester 1
measure: Subject Incidence With Bleeding - Trimester 2 (Safety Pop.)
timeFrame: Trimester 2
measure: Subject Incidence With Bleeding - Trimester 3 (Safety Pop.)
timeFrame: Trimester 3
measure: Subject Incidence With Bleeding - Trimester 4 (Safety Pop.)
timeFrame: Trimester 4
measure: Number of Days With Bleeding - Trimester 1 (Safety Pop.)
timeFrame: Trimester 1
measure: Number of Days With Bleeding - Trimester 2 (Safety Pop.)
timeFrame: Trimester 2
measure: Number of Days With Bleeding - Trimester 3 (Safety Pop.)
timeFrame: Trimester 3
measure: Number of Days With Bleeding - Trimester 4 (Safety Pop.)
timeFrame: Trimester 4
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)
timeFrame: Baseline and Month 12
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)
timeFrame: Baseline and Week 12
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)
timeFrame: Baseline and Month 6
measure: Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)
timeFrame: Baseline and Month 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Simon Williamson Clinic
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Mobile
country: United States
facility: Mobile Ob-Gyn, P.C.
state: Alabama
city: Montgomery
country: United States
facility: Montgomery Women's Health
state: Alabama
city: Glendale
country: United States
facility: Advanced Research Associates
state: Arizona
city: Mesa
country: United States
facility: Cactus Clinical Research
state: Arizona
city: Phoenix
country: United States
facility: Precision Trials
state: Arizona
city: Tucson
country: United States
facility: Radiant Research (Tucson)
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research Tucson
state: Arizona
city: Hot Springs
country: United States
facility: Health Star Research, LLC
state: Arkansas
city: Berkeley
country: United States
facility: Sutter East Bay Medical Foundation
state: California
city: La Mesa
country: United States
facility: Grossmont Center for Clinical Research
state: California
city: Norwalk
country: United States
facility: Futura Research
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Women's Health Care Research Corp.
state: California
city: Santa Rosa
country: United States
facility: Radiant Research, Inc.
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Denver
country: United States
facility: Downtown Women's Healthcare
state: Colorado
city: Denver
country: United States
facility: Horizon's Clinical Research Center
state: Colorado
city: Lakewood
country: United States
facility: Red Rocks OB/Gyn
state: Colorado
city: Milford
country: United States
facility: Clinical Research Consulting
state: Connecticut
city: New London
country: United States
facility: Coastal Connecticut Research
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Gainesville
country: United States
facility: Southeastern Integrated Medical, PL, d/b/a Florida Medical Research
state: Florida
city: Jacksonville
country: United States
facility: UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology
state: Florida
city: Margate
country: United States
facility: Suncoast Research
state: Florida
city: Melbourne
country: United States
facility: Accelovance
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc
state: Florida
city: North Miami Beach
country: United States
facility: Ideal Clinical Research
state: Florida
city: North Miami
country: United States
facility: Segal Institute
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Pinellas Park
country: United States
facility: Radiant Research (St. Petersburg)
state: Florida
city: Plantation
country: United States
facility: All Women's Healthcare of West Broward Discovery Clinical Research
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials
state: Florida
city: Atlanta
country: United States
facility: Radiant Research (Atlanta)
state: Georgia
city: Atlanta
country: United States
facility: Women's Health Associates
state: Georgia
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Sandy Springs
country: United States
facility: Wake Research - Mount Vernon Clinical Research
state: Georgia
city: Savannah
country: United States
facility: Fellows Research Alliance
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials
state: Idaho
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Addison
country: United States
facility: Biofortis
state: Illinois
city: Champaign
country: United States
facility: Women's Health Practice
state: Illinois
city: Chicago
country: United States
facility: Radiant Research (Chicago)
state: Illinois
city: Granger
country: United States
facility: The South Bend Clinic Granger
state: Indiana
city: Indianapolis
country: United States
facility: Davis Clinic
state: Indiana
city: Wichita
country: United States
facility: Cypress Medical Research Center, LLC
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Associates
state: Kentucky
city: Louisville
country: United States
facility: Bluegrass Clinical Research
state: Kentucky
city: Eunice
country: United States
facility: Horizon Research Group
state: Louisiana
city: Lutherville
country: United States
facility: Maryland Center for Sexual Health
state: Maryland
city: Bingham Farms
country: United States
facility: Quest Research Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Female Pelvic Medicine & Urogynecology
state: Michigan
city: Kalamazoo
country: United States
facility: Beyer Research
state: Michigan
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group
state: Michigan
city: Saint Louis
country: United States
facility: Radiant Research (St. Louis)
state: Missouri
city: Billings
country: United States
facility: Billings Clinical Research
state: Montana
city: Billings
country: United States
facility: Montana Health
state: Montana
city: Lincoln
country: United States
facility: Women's Clinic of Lincoln
state: Nebraska
city: Las Vegas
country: United States
facility: Affiliated Clinical Research INC
state: Nevada
city: Las Vegas
country: United States
facility: Affiliated Clinical Research
state: Nevada
city: Lawrenceville
country: United States
facility: Lawrence OB-GYN Clinical Research
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Albuquerque
country: United States
facility: Bosque Women's Care
state: New Mexico
city: Albuquerque
country: United States
facility: Southwest Clinical Research
state: New Mexico
city: New York
country: United States
facility: Columbia University
state: New York
city: Port Jefferson
country: United States
facility: Suffolk OB/GYN
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Durham
country: United States
facility: Women's Wellness Clinic
state: North Carolina
city: High Point
country: United States
facility: Carolina Medical Trials
state: North Carolina
city: Raleigh
country: United States
facility: Centre OBGYN
state: North Carolina
city: Raleigh
country: United States
facility: Wake County Research
state: North Carolina
city: Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Carolina Medical Trials
state: North Carolina
city: Winston-Salem
country: United States
facility: Hawthorne Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Triad Ob-Gyn
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research
state: North Dakota
city: Akron
country: United States
facility: Radiant Research (Akron)
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Company
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research
state: Ohio
city: Columbus
country: United States
facility: Columbus Center for Women's Health Research
state: Ohio
city: Englewood
country: United States
facility: HWC Women's Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Medford
country: United States
facility: Sunstone Medical Research
state: Oregon
city: Jenkintown
country: United States
facility: The Clinical Trial Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Clinical Trials Research Services, LLC
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Bluffton
country: United States
facility: Fellows Research Group
state: South Carolina
city: Columbia
country: United States
facility: Vista Clinical Research
state: South Carolina
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group/NOCCR
state: Tennessee
city: Bryan
country: United States
facility: DiscoveResearch, Inc.
state: Texas
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Fort Worth
country: United States
facility: Brownstone Clinical Trials
state: Texas
city: Houston
country: United States
facility: Advances in Health
state: Texas
city: Houston
country: United States
facility: The Women's Hospital of Texas
state: Texas
city: Houston
country: United States
facility: TMC Life Research
state: Texas
city: Hurst
country: United States
facility: Protenium Clinical Research
state: Texas
city: Irving
country: United States
facility: MacArthur OB/GYN
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: San Antonio
country: United States
facility: Stone Oak, LLC dba Discovery Clinical Trials
state: Texas
city: Schertz
country: United States
facility: NECRSA
state: Texas
city: Draper
country: United States
facility: PRO/ Salt Lake Women's Center
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
city: Charlottesville
country: United States
facility: UVA/Midlife Health at North Ridge
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Center Eastern Virginia Medical School
state: Virginia
city: Richmond
country: United States
facility: Virginia Women's Center
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research-Richmond, Inc
state: Virginia
city: Virginia Beach
country: United States
facility: Tidewater Clinical Research
state: Virginia
city: Seattle
country: United States
facility: Seattle Women's Health Research, Gynecology
state: Washington
city: Spokane
country: United States
facility: North Spokane Women's Health
state: Washington
Study officials:
affiliation: TherapeuticsMD
name: Sebastian Mirkin, MD
role: STUDY_DIRECTOR
References:
citation: Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161-75. doi: 10.1016/s0378-5122(96)82006-8.
citation: Gerlinger C, Gude K, Hiemeyer F, Schmelter T, Schafers M. An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women. Menopause. 2012 Jul;19(7):799-803. doi: 10.1097/gme.0b013e31823de8ba.
citation: Spritzer, K. L. & Hays, R. D. (2003, November). MOS Sleep Scale: A Manual for Use and Scoring, Version 1.0. Los Angeles, CA.
citation: Kurman RJ, Ellenson L H, and Ronnett B.M., ed. Blaustein's Pathology of the Female Genital Tract. 6th ed. New York, NY: Springer; 2011:305-452.
citation: Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008 Feb;61(2):102-9. doi: 10.1016/j.jclinepi.2007.03.012. Epub 2007 Aug 3.
citation: Hays RD and Stewart AL. Sleep measures. In AL Stewart & JE Ware (eds), Measuring functioning and well-being: The Medical Outcomes Study approach (pp 235-259). Durham, NC: Duke University Press, 1992.
citation: McClung MR, Kagan R, Graham S, Bernick B, Mirkin S, Constantine G. Effects of E2/P4 oral capsules on bone turnover in women with vasomotor symptoms. Menopause. 2022 Feb 14;29(3):304-308. doi: 10.1097/GME.0000000000001915.
citation: Constantine GD, Simon JA, Kaunitz AM, Pickar JH, Revicki DA, Graham S, Bernick B, Mirkin S. TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial. Menopause. 2020 Nov;27(11):1236-1241. doi: 10.1097/GME.0000000000001602.
citation: Black DR, Minkin MJ, Graham S, Bernick B, Mirkin S. Effects of combined 17beta-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial. Menopause. 2020 Sep 14;28(1):32-39. doi: 10.1097/GME.0000000000001659.
citation: Kaunitz AM, Bitner D, Constantine GD, Bernick B, Graham S, Mirkin S. 17beta-estradiol/progesterone in a single, oral, softgel capsule (TX-001HR) significantly increased the number of vasomotor symptom-free days in the REPLENISH trial. Menopause. 2020 Dec;27(12):1382-1387. doi: 10.1097/GME.0000000000001615.
citation: Mirkin S, Goldstein SR, Archer DF, Pickar JH, Graham S, Bernick B. Endometrial safety and bleeding profile of a 17beta-estradiol/progesterone oral softgel capsule (TX-001HR). Menopause. 2020 Apr;27(4):410-417. doi: 10.1097/GME.0000000000001480.
citation: Lobo RA, Kaunitz AM, Santoro N, Bernick B, Graham S, Mirkin S. Metabolic and cardiovascular effects of TX-001HR in menopausal women with vasomotor symptoms. Climacteric. 2019 Dec;22(6):610-616. doi: 10.1080/13697137.2019.1640197. Epub 2019 Jul 31.
citation: Mirkin S, Graham S, Revicki DA, Bender RH, Bernick B, Constantine GD. Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17beta-estradiol/progesterone. Menopause. 2019 Jan 9;26(6):637-642. doi: 10.1097/GME.0000000000001294.
citation: Kagan R, Constantine G, Kaunitz AM, Bernick B, Mirkin S. Improvement in sleep outcomes with a 17beta-estradiol-progesterone oral capsule (TX-001HR) for postmenopausal women. Menopause. 2018 Dec 21;26(6):622-628. doi: 10.1097/GME.0000000000001278.
citation: Lobo RA, Archer DF, Kagan R, Kaunitz AM, Constantine GD, Pickar JH, Graham S, Bernick B, Mirkin S. A 17beta-Estradiol-Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women: A Randomized Controlled Trial. Obstet Gynecol. 2018 Jul;132(1):161-170. doi: 10.1097/AOG.0000000000002645.
citation: Mirkin S, Amadio JM, Bernick BA, Pickar JH, Archer DF. 17beta-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. Maturitas. 2015 May;81(1):28-35. doi: 10.1016/j.maturitas.2015.02.266. Epub 2015 Mar 9.