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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02253173
Other study ID # TXV14-01
Secondary ID
Status Completed
Phase Phase 3
First received September 26, 2014
Last updated November 2, 2015
Start date September 2014
Est. completion date October 2015

Study information

Verified date November 2015
Source TherapeuticsMD
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of a new formulation of vaginal estradiol for the treatment of symptoms of vulvar and vaginal atrophy in postmenopausal women.


Recruitment information / eligibility

Status Completed
Enrollment 764
Est. completion date October 2015
Est. primary completion date October 2015
Accepts healthy volunteers No
Gender Female
Age group 40 Years to 75 Years
Eligibility Inclusion Criteria:

1. Postmenopausal female subjects between the ages of 40 and 75 years (at the time of randomization) with at least:

- 12 months of spontaneous amenorrhea (women <55 years of age with a history of hysterectomy without bilateral oophorectomy prior to natural menopause must have follicle stimulating hormone (FSH) levels > 40 mIU/mL), OR

- 6 months of spontaneous amenorrhea with follicle stimulating hormone (FSH) levels > 40mlU/mL OR

- At least 6 weeks postsurgical bilateral oophorectomy.

2. =5% superficial cells on vaginal cytological smear

3. Vaginal pH > 5.0

4. Moderate to severe symptom of vaginal pain associated with sexual activity considered the most bothersome vaginal symptom by the subject at screening visit 1A.

5. Moderate to severe symptom of vaginal pain associated with sexual activity at screening visit 1B.

6. Onset of moderate to severe dyspareunia in the postmenopausal years.

7. Subjects should be sexually active (i.e. have sexual activity with vaginal penetration within approximately 1 month of screening visit 1A).

8. Subjects should anticipate having sexual activity (with vaginal penetration) during the conduct of the trial.

9. For subjects with an intact uterus: Subjects must have an acceptable result from an evaluable screening endometrial biopsy.

10. Subjects who have a Body Mass Index (BMI) less than or equal to 38 kg/m2. BMI values should be rounded to the nearest integer (ex. 32.4 rounds down to 32, while 26.5 rounds up to 27).

11. In the opinion of the investigator, the subject will comply with the protocol and has a high probability of completing the study.

Exclusion Criteria:

1. Use of the following:

1. Oral estrogen-, progestin-, androgen-, or SERM-containing drug products within 8 weeks before screening visit 1A (can enter washout);

2. Use of transdermal hormone products within 4 weeks before screening visit 1A (can enter washout);

3. Use of vaginal hormone products (rings, creams, gels) within 4 weeks before screening visit1A (can enter washout);

4. Use of intrauterine progestins within 8 weeks before screening visit 1A (can enter washout);

5. Use of progestin implants/injectables or estrogen pellets/injectables within 6 months before screening visit 1A (cannot enter washout);

6. Use of vaginal lubricants or moisturizers within 7 days before the screening visit 1B vaginal pH assessment.

2. A history or active presence of clinically important medical disease that might confound the study or be detrimental to the subject, examples include:

1. Hypersensitivity to estrogens;

2. Endometrial hyperplasia;

3. Undiagnosed vaginal bleeding;

4. Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure);

5. Thrombophlebitis, thrombosis or thromboembolic disorders;

6. Cerebrovascular accident, stroke, or transient ischemic attack;

7. Myocardial infarction or ischemic heart disease;

8. Malignancy or treatment for malignancy, within the previous 5 years, with the exception of basal cell carcinoma of the skin or squamous cell carcinoma of the skin. A history of estrogen dependent neoplasia, breast cancer, melanoma or any gynecologic cancer, at any time, excludes the subject;

9. Endocrine disease (except for controlled hypothyroidism or controlled non-insulin dependent diabetes mellitus).

3. Recent history of known alcohol or drug abuse.

4. History of sexual abuse or spousal abuse that, in the opinion of the PI, may interfere with the subject's assessment of vaginal pain with sexual activity.

5. Current history of Heavy smoking (more than 15 cigarettes per day) or use of e-cigarettes.

6. Use of an intrauterine device within 12 weeks before screening visit 1A.

7. Use of an investigational drug within 60 days before screening visit 1A.

8. Any clinically important abnormalities on screening physical exam, assessments, ECG, or laboratory tests, such as:

1. Unresolved cervical cytologic smear report of atypical glandular cells of undetermined significance (AGUS) or atypical squamous cells of undetermined significance (ASCUS).

Cervical cytologic smear report of low-grade squamous intraepithelial lesion (SIL) or greater, CIN1 or greater, or any reported dysplasia; Subjects with ASCUS are eligible only if high risk human papilloma virus (HPV) result is negative.

2. Unresolved findings suspicious for malignancy on the breast exam; incomplete mammogram result (BI-RADS 0) or unresolved findings suggestive of malignant changes or findings requiring short interval follow-up on the prestudy mammogram (subjects must have mammography result of BI-RADS 1 or 2 to enroll.) Mammogram may be performed within 9 months prior to Visit 2 (randomization) with documentation available. (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);

3. In subjects with intact uterus: 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);

4. In subjects with intact uterus: an endometrial biopsy report by one central pathologist at screening with one of the following:

- Endometrial hyperplasia endometrial cancer, proliferative endometrium, weakly proliferative endometrium, disordered proliferative pattern; OR

- Endometrial polyps with hyperplasia, glandular atypia of any degree (e.g., atypical nuclei) or cancer;

5. Vulvar or vaginal inflammatory condition such as a contact or allergic dermatitis, lichen sclerosis or other pathological findings;

6. Presence of suspicious vulvar or vaginal lesions for dysplasia, malignancy or other pathology other than atrophy;

7. Painful genital warts or localized areas of ulceration;

8. A history of active, chronic pelvic pain;

9. Interstitial cystitis;

10. Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal for the laboratory used;

11. Fasting total cholesterol greater than 300 mg/dL (7.77 mmol/L) or triglycerides greater than 300 mg/dL (3.39 mmol/L);

12. Fasting blood glucose greater than 125 mg/dL (6.94 mmol/L) with a hemoglobin A1C of greater than or equal to 6.5%;

13. Uncontrolled hypertension; subjects with elevated sitting blood pressure, greater than 140 mm Hg systolic or greater than 90 mm Hg diastolic and may not be using more than 2 antihypertensive medications for the treatment of hypertension;

14. Clinically significant abnormal 12-lead ECG (such as myocardial infarction or other findings suggestive of ischemia)

9. 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, hysterectomy, or are 55 years old or greater and have experienced cessation of menses for at least 1 year.

10. Current use of marijuana.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
Estradiol

Placebo


Locations

Country Name City State
Canada Diex Research Montreal Inc. Montreal Quebec
Canada Center for Research Saint-Louis Quebec
Canada Clinique RSF Inc. Quebec
Canada Diex Research Sherbrooke Inc. Sherbrooke Quebec
Canada Manna Research Inc St-Romuald Quebec
United States Radiant Research Akron Ohio
United States Bosque Women's Care Albuquerque New Mexico
United States Southwest Clinical Research Albuquerque New Mexico
United States ClinSite, LLC Ann Arbor Michigan
United States Women's Health Associates Atlanta Georgia
United States Masters of Clinical Research, Inc. Augusta Georgia
United States South Florida Medical Research Aventura Florida
United States American Health Network of Indiana, LLC Avon Indiana
United States Sutter East Bay Medical Foundation Berkeley California
United States Montana Health Billings Montana
United States Fellows Research Alliance, Inc. Bluffton South Carolina
United States Advanced Clinical Research Boise Idaho
United States Chattanooga Medical Research Chattanooga Tennessee
United States Radiant Research Chicago Illinois
United States University of Cincinnati Physicians Company Cincinnati Ohio
United States Rapid Medical Research Cleveland Ohio
United States Lynn Institute of the Rockies Colorado Springs Colorado
United States Vista Clinical Research Columbia South Carolina
United States Columbus Center for Women's Health Research Columbus Ohio
United States Advanced Research Associates Corpus Christi Texas
United States Nature Coast Clinical Research Crystal River Florida
United States Research Across America Dallas Texas
United States UT Southwestern Medical Center Dallas Texas
United States Soapstone Center for Clinical Research Decatur Georgia
United States Avail Clinical Research DeLand Florida
United States Downtown Women's Health Care Denver Colorado
United States Horizons Clinical Research Center Denver Colorado
United States Women's Wellness Clinic Durham North Carolina
United States HWC Women's Research Center Englewood Ohio
United States Horizon Research Group of Opelousas Eunice Louisiana
United States Lillestol Research Fargo North Dakota
United States Clinical Physiology Associates Fort Myers Florida
United States Capital Women's Care Frederick Maryland
United States UF Health Physicians Women's & REI Springhill Gainesville Florida
United States Pinewest OB-GYN, Inc. High Point North Carolina
United States Advances in Health Houston Texas
United States Hwca, Pllc Houston Texas
United States TMC Life Research Houston Texas
United States Medical Affiliated Research Center Huntsville Alabama
United States Women's Healthcare Associates P.A. Idaho Falls Idaho
United States Jacksonville Center for Clinical Research Jacksonville Florida
United States UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology Jacksonville Florida
United States The Clinical Trial Center Jenkintown Pennsylvania
United States Beyer Research Kalamazoo Michigan
United States Lafayette Clinical Research Group Lafayette Indiana
United States Red Rocks OB/Gyn Lakewood Colorado
United States Office of Edmond E. Pack, MD Las Vegas Nevada
United States Office of R. Garn Mabey, MD Las Vegas Nevada
United States Lawrence OB-GYN Clinical Research, LLC Lawrenceville New Jersey
United States Central Kentucky Research Associates, Inc. Lexington Kentucky
United States Women's Clinic of Lincoln Lincoln Nebraska
United States Torrance Clinical Research Institute Inc Lomita California
United States Bluegrass Clinical Research, Inc. Louisville Kentucky
United States Maryland Center for Sexual Health Lutherville Maryland
United States South Florida Wellness & Clinical Research Institute Margate Florida
United States Landerbrook Health Center Mayfield Heights Ohio
United States Sunstone Medical Research Medford Oregon
United States Cactus Clinical Research Meza Arizona
United States New Age Medical Research Corporation Miami Florida
United States Clinical Research Consulting Milford Connecticut
United States Montogomery Women's Health Montgomery Alabama
United States Coastal Carolina Research Center Mt. Pleasant South Carolina
United States Rutgers-Robert Wood Johnson Medical School New Brunswick New Jersey
United States Coastal Connecticut Research, LLC New London Connecticut
United States Suncoast Clinical Research, Inc. New Port Richey Florida
United States Columbia University Medical Center New York New York
United States Clinical Research Center, EVMS Norfolk Virginia
United States National Clinical Research-Norfolk Norfolk Virginia
United States Healthcare Clinical Data North Miami Florida
United States Ideal Clinical Research North Miami Beach Florida
United States Futura Research Norwalk California
United States Clinical Research of Philadelphia Philadelphia Pennsylvania
United States Arizona Wellness Center for Women Phoenix Arizona
United States Radiant Research Pinellas Park Florida
United States Clinical Trials Research Services Pittsburgh Pennsylvania
United States Women's Health Research Center Plainsboro New Jersey
United States All Women's Healthcare of West Broward Plantation Florida
United States Suffolk OB/GYN Port Jefferson New York
United States Wake Research Associates Raleigh North Carolina
United States National Clinical Research-Richmond, Inc Richmond Virginia
United States Virginia Women's Center, Inc. Richmond Virginia
United States Northern California Research Sacramento California
United States Saginaw Valley Medical Research Group, L.L.C. Saginaw Michigan
United States Stone Oak, LLC dba Discovery Clinical Trials San Antonio Texas
United States Medical Center for Clinical Research San Diego California
United States San Diego Sexual Medicine San Diego California
United States Women's Health Care Research Corp. San Diego California
United States WR-Mount Vernon Clinical Research Sandy Springs Georgia
United States Physician Care Clinical Research Sarasota Florida
United States Fellows Research Alliance, Inc. Savannah Georgia
United States Radiant Research Scottsdale Arizona
United States Seattle Women's Health, Research, and Gynecology Seattle Washington
United States North Spokane Women's Health Spokane Washington
United States Visions Clinical Research - Tucson Tucson Arizona
United States Tidewater Clinical Research Virginia Beach Virginia
United States James A. Simon, Women's Health & Research Consultants Washington District of Columbia
United States Comprehensive Clinical Trials West Palm Beach Florida
United States Cypress Medical Research Center Wichita Kansas
United States Hawthorne Research Winston-Salem North Carolina
United States Lyndhurst Clinical Research Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
TherapeuticsMD

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other Safety Endpoints - Adverse Events, Vital Signs, Physical Exam Findings, Gynecological Exam Findings, Clinical Lab Tests, Endometrial Biopsies Adverse events and serious adverse events (SAEs) will be summarized for each treatment group and overall for all active treatment groups with the proportion of subjects reporting each event. Actual values and change from baseline in vital signs, and all laboratory test parameters will be summarized for each treatment group and overall for all active treatment groups with descriptive statistics at each assessment obtained. The incidence rate for endometrial hyperplasia will be calculated for each treatment group. 12 Weeks Yes
Primary Co-Primary Efficacy Endpoint - Vaginal Superficial Cells • Change from baseline to week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo 12 Weeks No
Primary Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells • Change from baseline to week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo 12 Weeks No
Primary Co-Primary Efficacy Endpoint - Vaginal pH • Change from baseline to week 12 in vaginal pH as compared to placebo 12 Weeks No
Primary Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia) • Change from baseline to week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo 12 Weeks No
Secondary Secondary Efficacy Endpoints - Vaginal Superficial and Parabasal Cells, Vaginal pH and Severity of MBS (dyspareunia) Change from baseline to weeks 2, 6, and 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Change from baseline to weeks 2, 6 and 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Change from baseline to weeks 2, 6 and 8 in vaginal pH as compared to placebo
Change from baseline to weeks 2, 6 and 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo
2, 6 and 8 Weeks No
Secondary Secondary Efficacy Endpoints - Severity of other VVA symptoms and visual evaluation of vaginal mucosa Change from baseline to weeks 2, 6, 8 and 12 on the severity of the vaginal dryness and vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo
Change in visual evaluation of the vaginal mucosa from baseline to weeks 2, 6, 8 and 12 compared to placebo
2, 6, 8 and 12 Weeks No
Secondary Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) • Change from baseline in the FSFI at week 12 compared to placebo 12 Weeks No
Secondary Secondary Efficacy Endpoints - Hormone Concentration Assessments (serum estradiol, estrone and estrone conjugates; SHBG) - PK Substudy Blood samples will be obtained from a subset of subjects at pre-selected sites to characterize PK parameters (AUC, tmax, Cmin, Cmax) and to measure SHBG Pre-treatment, Day 1, Weeks 2 and 12 No
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