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Vulvovaginal AtrophyPhase 3REJOICENCT02253173

Estradiol Vaginal Softgel Capsules in Treating Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women

A Phase 3 study testing Estradiol in people with Vulvovaginal Atrophy and Menopause, run by TherapeuticsMD at 105 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 40 to 75 years, women only
Conditions the study is for
Vulvovaginal Atrophy, Menopause, Dyspareunia
What is being tested?
Estradiol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
764 participants
Where
105 sitesin 2 countries
Study dates
Sep 2014to Oct 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • ≤5% superficial cells on vaginal cytological smear
  • Vaginal pH > 5.0
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  • Moderate to severe symptom of vaginal pain associated with sexual activity considered the most bothersome vaginal symptom by the subject at screening visit 1A.
  • Moderate to severe symptom of vaginal pain associated with sexual activity at screening visit 1B.
  • Onset of moderate to severe dyspareunia in the postmenopausal years.
  • Subjects should be sexually active (i.e. have sexual activity with vaginal penetration within approximately 1 month of screening visit 1A).
  • Subjects should anticipate having sexual activity (with vaginal penetration) during the conduct of the trial.
  • For subjects with an intact uterus: Subjects must have an acceptable result from an evaluable screening endometrial biopsy.
  • 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).
  • In the opinion of the investigator, the subject will comply with the protocol and has a high probability of completing the study.

Who cannot join

  • Use of the following:
  • Oral estrogen-, progestin-, androgen-, or SERM-containing drug products within 8 weeks before screening visit 1A (can enter washout);
  • Use of transdermal hormone products within 4 weeks before screening visit 1A (can enter washout);
  • Use of vaginal hormone products (rings, creams, gels) within 4 weeks before screening visit1A (can enter washout);
  • Use of intrauterine progestins within 8 weeks before screening visit 1A (can enter washout);
  • Use of progestin implants/injectables or estrogen pellets/injectables within 6 months before screening visit 1A (cannot enter washout);
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  • Use of vaginal lubricants or moisturizers within 7 days before the screening visit 1B vaginal pH assessment.
  • A history or active presence of clinically important medical disease that might confound the study or be detrimental to the subject, examples include:
  • Hypersensitivity to estrogens;
  • Endometrial hyperplasia;
  • Undiagnosed vaginal bleeding;
  • Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure);
  • Thrombophlebitis, thrombosis or thromboembolic disorders;
  • Cerebrovascular accident, stroke, or transient ischemic attack;
  • Myocardial infarction or ischemic heart disease;
  • 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;
  • Endocrine disease (except for controlled hypothyroidism or controlled non-insulin dependent diabetes mellitus).
  • Recent history of known alcohol or drug abuse.
  • 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.
  • Current history of Heavy smoking (more than 15 cigarettes per day) or use of e-cigarettes.
  • Use of an intrauterine device within 12 weeks before screening visit 1A.
  • Use of an investigational drug within 60 days before screening visit 1A.
  • Any clinically important abnormalities on screening physical exam, assessments, ECG, or laboratory tests, such as:
  • 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.
  • 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);
  • 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);
  • 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;
  • Vulvar or vaginal inflammatory condition such as a contact or allergic dermatitis, lichen sclerosis or other pathological findings;
  • Presence of suspicious vulvar or vaginal lesions for dysplasia, malignancy or other pathology other than atrophy;
  • Painful genital warts or localized areas of ulceration;
  • A history of active, chronic pelvic pain;
  • Interstitial cystitis;
  • Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) greater than 1.5 times the upper limit of normal for the laboratory used;
  • Fasting total cholesterol greater than 300 mg/dL (7.77 mmol/L) or triglycerides greater than 300 mg/dL (3.39 mmol/L);
  • Fasting blood glucose greater than 125 mg/dL (6.94 mmol/L) with a hemoglobin A1C of greater than or equal to 6.5%;
  • 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;
  • Clinically significant abnormal 12-lead ECG (such as myocardial infarction or other findings suggestive of ischemia)
  • 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.
  • Current use of marijuana.

Trial locations and contacts

105 sites in 2 countries.

105 sites in 2 countries

United States100 sites
  • Radiant Research

    Akron, Ohio, 44311

  • Bosque Women's Care

    Albuquerque, New Mexico, 87109

  • Southwest Clinical Research

    Albuquerque, New Mexico, 87109

  • ClinSite, LLC

    Ann Arbor, Michigan, 48106

  • Women's Health Associates

    Atlanta, Georgia, 30342

  • Masters of Clinical Research, Inc.

    Augusta, Georgia, 30909

  • South Florida Medical Research

    Aventura, Florida, 33180

  • American Health Network of Indiana, LLC

    Avon, Indiana, 46123

  • Sutter East Bay Medical Foundation

    Berkeley, California, 94705

  • Montana Health

    Billings, Montana, 59102

  • Fellows Research Alliance, Inc.

    Bluffton, South Carolina, 29910

  • Advanced Clinical Research

    Boise, Idaho, 83642

  • Chattanooga Medical Research

    Chattanooga, Tennessee, 37404

  • Radiant Research

    Chicago, Illinois, 60654

  • University of Cincinnati Physicians Company

    Cincinnati, Ohio, 45267-0457

  • Rapid Medical Research

    Cleveland, Ohio, 44122

  • Lynn Institute of the Rockies

    Colorado Springs, Colorado, 80909

  • Vista Clinical Research

    Columbia, South Carolina, 29201

  • Columbus Center for Women's Health Research

    Columbus, Ohio, 43213

  • Advanced Research Associates

    Corpus Christi, Texas, 78414

  • Nature Coast Clinical Research

    Crystal River, Florida, 34429

  • Research Across America

    Dallas, Texas, 75234

  • UT Southwestern Medical Center

    Dallas, Texas, 75390-9032

  • Soapstone Center for Clinical Research

    Decatur, Georgia, 30034

  • Avail Clinical Research

    DeLand, Florida, 32720

  • Downtown Women's Health Care

    Denver, Colorado, 80209

  • Horizons Clinical Research Center

    Denver, Colorado, 80220

  • Women's Wellness Clinic

    Durham, North Carolina, 27713

  • HWC Women's Research Center

    Englewood, Ohio, 45322

  • Horizon Research Group of Opelousas

    Eunice, Louisiana, 70535

  • Lillestol Research

    Fargo, North Dakota, 58103

  • Clinical Physiology Associates

    Fort Myers, Florida, 33916

  • Capital Women's Care

    Frederick, Maryland, 21702

  • UF Health Physicians Women's & REI Springhill

    Gainesville, Florida, 32606

  • Pinewest OB-GYN, Inc.

    High Point, North Carolina, 27262

  • Advances in Health

    Houston, Texas, 77030

  • Hwca, Pllc

    Houston, Texas, 77054

  • TMC Life Research

    Houston, Texas, 77054

  • Medical Affiliated Research Center

    Huntsville, Alabama, 35801

  • Women's Healthcare Associates P.A.

    Idaho Falls, Idaho, 83404

  • UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology

    Jacksonville, Florida, 32207

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • The Clinical Trial Center

    Jenkintown, Pennsylvania, 19046

  • Beyer Research

    Kalamazoo, Michigan, 49009

  • Lafayette Clinical Research Group

    Lafayette, Indiana, 47905

  • Red Rocks OB/Gyn

    Lakewood, Colorado, 80228

  • Office of Edmond E. Pack, MD

    Las Vegas, Nevada, 89113

  • Office of R. Garn Mabey, MD

    Las Vegas, Nevada, 89128

  • Lawrence OB-GYN Clinical Research, LLC

    Lawrenceville, New Jersey, 08648

  • Central Kentucky Research Associates, Inc.

    Lexington, Kentucky, 40509

  • Women's Clinic of Lincoln

    Lincoln, Nebraska, 68510

  • Torrance Clinical Research Institute Inc

    Lomita, California, 90717

  • Bluegrass Clinical Research, Inc.

    Louisville, Kentucky, 40291

  • Maryland Center for Sexual Health

    Lutherville, Maryland, 21093

  • South Florida Wellness & Clinical Research Institute

    Margate, Florida, 33063

  • Landerbrook Health Center

    Mayfield Heights, Ohio, 44124

  • Sunstone Medical Research

    Medford, Oregon, 97504

  • Cactus Clinical Research

    Mesa, Arizona, 85209

  • New Age Medical Research Corporation

    Miami, Florida, 33186

  • Clinical Research Consulting

    Milford, Connecticut, 06460

  • Montogomery Women's Health

    Montgomery, Alabama, 36117

  • Coastal Carolina Research Center

    Mt. Pleasant, South Carolina, 29464

  • Rutgers-Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08901

  • Coastal Connecticut Research, LLC

    New London, Connecticut, 06320

  • Suncoast Clinical Research, Inc.

    New Port Richey, Florida, 34652

  • Columbia University Medical Center

    New York, New York, 10032

  • National Clinical Research-Norfolk

    Norfolk, Virginia, 23502

  • Clinical Research Center, EVMS

    Norfolk, Virginia, 23507

  • Healthcare Clinical Data

    North Miami, Florida, 33161

  • Ideal Clinical Research

    North Miami Beach, Florida, 33162

  • Futura Research

    Norwalk, California, 90650

  • Clinical Research of Philadelphia

    Philadelphia, Pennsylvania, 19114

  • Arizona Wellness Center for Women

    Phoenix, Arizona, 85032

  • Radiant Research

    Pinellas Park, Florida, 33781

  • Clinical Trials Research Services

    Pittsburgh, Pennsylvania, 15206

  • Women's Health Research Center

    Plainsboro, New Jersey, 08536

  • All Women's Healthcare of West Broward

    Plantation, Florida, 33324

  • Suffolk OB/GYN

    Port Jefferson, New York, 08536

  • Wake Research Associates

    Raleigh, North Carolina, 27612

  • Virginia Women's Center, Inc.

    Richmond, Virginia, 23233

  • National Clinical Research-Richmond, Inc

    Richmond, Virginia, 23294

  • Northern California Research

    Sacramento, California, 95821

  • Saginaw Valley Medical Research Group, L.L.C.

    Saginaw, Michigan, 48604

  • Stone Oak, LLC dba Discovery Clinical Trials

    San Antonio, Texas, 78258

  • Medical Center for Clinical Research

    San Diego, California, 92108

  • San Diego Sexual Medicine

    San Diego, California, 92120

  • Women's Health Care Research Corp.

    San Diego, California, 92123

  • WR-Mount Vernon Clinical Research

    Sandy Springs, Georgia, 30328

  • Physician Care Clinical Research

    Sarasota, Florida, 34239

  • Fellows Research Alliance, Inc.

    Savannah, Georgia, 31046

  • Radiant Research

    Scottsdale, Arizona, 85251

  • Seattle Women's Health, Research, and Gynecology

    Seattle, Washington, 98105

  • North Spokane Women's Health

    Spokane, Washington, 99207

  • Visions Clinical Research - Tucson

    Tucson, Arizona, 85712

  • Tidewater Clinical Research

    Virginia Beach, Virginia, 23456

  • James A. Simon, Women's Health & Research Consultants

    Washington D.C., District of Columbia, 20036

  • Comprehensive Clinical Trials

    West Palm Beach, Florida, 33409

  • Cypress Medical Research Center

    Wichita, Kansas, 67226

  • Hawthorne Research

    Winston-Salem, North Carolina, 27103

  • Lyndhurst Clinical Research

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada5 sites
  • Diex Research Montreal Inc.

    Montreal, Quebec, H4N 3C5

  • Center for Research Saint-Louis

    Québec, Quebec, G1W4R4

  • Clinique RSF Inc.

    Québec, G1S 2L6

  • Manna Research Inc

    Saint Romuald, Quebec, G6W 5M6

  • Diex Research Sherbrooke Inc.

    Sherbrooke, Quebec, J1H 1Z1

Other trials in Canada

About this study

Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Trial to Evaluate the Safety and Efficacy of TX-004HR in Postmenopausal Women With Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy

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.

Being tested
Estradiol, Placebo
Keywords
VVA, Painful Sex, Postmenopausal
Medical subject headings
Dyspareunia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EstradiolDrug

  • PlaceboDrug

Study groups in NCT02253173
Study groupRoleWhat they receive
Estradiol 4mcg Vaginal Softgel CapsuleExperimentalEstradiol 4mcg Vaginal Softgel Capsule
Receives: Drug: Estradiol
Estradiol 10mcg Vaginal Softgel CapsuleExperimentalEstradiol 10mcg Vaginal Softgel Capsule
Receives: Drug: Estradiol
Estradiol 25mcg Vaginal Softgel CapsuleExperimentalEstradiol 25mcg Vaginal Softgel Capsule
Receives: Drug: Estradiol
Placebo Vaginal Softgel CapsulePlacebo comparatorPlacebo Vaginal Softgel Capsule
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline and 12 Weeks

  2. 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

    Measured: Baseline and 12 Weeks

  3. Co-Primary Efficacy Endpoint - Vaginal pH

    • Change from Baseline to Week 12 in vaginal pH as compared to placebo

    Measured: Baseline and 12 Weeks

  4. 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

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 12

    Measured: Baseline and Week 12

Secondary outcomes (43)
  1. Secondary Efficacy Endpoints - Vaginal Superficial Cells

    • Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 2

  2. Secondary Efficacy Endpoints- Vaginal Superficial Cells

    Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 6

  3. Secondary Efficacy Endpoints - Vaginal Superficial Cells

    Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 8

  4. Secondary Efficacy Endpoints - Vaginal Parabasal Cells

    Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 2

  5. Secondary Efficacy Endpoints - Vaginal Parabasal Cells

    Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 6

  6. Secondary Efficacy Endpoints - Vaginal Parabasal Cells

    Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

    Measured: Baseline and Week 8

  7. Secondary Efficacy Endpoints - Vaginal pH

    Change from Baseline to Week 2 in vaginal pH as compared to placebo

    Measured: Baseline and Week 2

  8. Secondary Efficacy Endpoints - Vaginal pH

    Change from Baseline to Week 6 in vaginal pH as compared to placebo

    Measured: Baseline and Week 6

  9. Secondary Efficacy Endpoints - Vaginal pH

    Change from Baseline to Week 8 in vaginal pH as compared to placebo

    Measured: Baseline and Week 8

  10. Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)

    Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 2

    Measured: Baseline and Week 2

  11. Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)

    Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 6

    Measured: Baseline and Week 6

  12. Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)

    Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 8

    Measured: Baseline and Week 8

  13. Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)

    Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 2

    Measured: Baseline and Week 2

  14. Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)

    Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 6

    Measured: Baseline and Week 6

  15. Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)

    Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 8

    Measured: Baseline and Week 8

  16. Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)

    Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 12

    Measured: Baseline and Week 12

  17. Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)

    Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 2

    Measured: Baseline and Week 2

  18. Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)

    Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 6

    Measured: Baseline and Week 6

  19. Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)

    Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 8

    Measured: Baseline and Week 8

  20. Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)

    Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

    VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

    Subjects assessed severity at Baseline and Week 12

    Measured: Baseline and Week 12

  21. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)

    Change from Baseline to Week 2 in Vaginal Color as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2

    Measured: Baseline and Week 2

  22. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)

    Change from Baseline to Week 6 in Vaginal Color as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6

    Measured: Baseline to Week 6

  23. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)

    Change from Baseline to Week 8 in Vaginal Color as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8

    Measured: Baseline to Week 8

  24. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)

    Change from Baseline to Week 12 in Vaginal Color as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12

    Measured: Baseline and Week 12

  25. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)

    Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

    Severity was assessed by the Investigator at Baseline and Week 2

    Measured: Baseline and Week 2

  26. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)

    Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

    Severity was assessed by the Investigator at Baseline and Week 6

    Measured: Baseline and Week 6

  27. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)

    Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

    Severity was assessed by the Investigator at Baseline and Week 8

    Measured: Baseline and Week 8

  28. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)

    Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

    Severity was assessed by the Investigator at Baseline and Week 12

    Measured: Baseline and Week 12

  29. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)

    Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

    Severity was assessed by the Investigator at Baseline and Week 2

    Measured: Baseline and Week 2

  30. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)

    Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

    Severity was assessed by the Investigator at Baseline and Week 6

    Measured: Baseline and Week 6

  31. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)

    Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

    Severity was assessed by the Investigator at Baseline and Week 8

    Measured: Baseline and Week 8

  32. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)

    Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

    Severity was assessed by the Investigator at Baseline and Week 12

    Measured: Baseline and Week 12

  33. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)

    Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3

    Severity was assessed by the Investigator at Baseline and Week 2

    Measured: Baseline and Week 2

  34. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)

    Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

    Severity was assessed by the Investigator at Baseline and Week 6

    Measured: Baseline and Week 6

  35. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)

    Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

    Severity was assessed by the Investigator at Baseline and Week 8

    Measured: Baseline and Week 8

  36. Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)

    Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo

    Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

    Severity was assessed by the Investigator at Baseline and Week 12

    Measured: Baseline and Week 12

  37. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score

    Change from Baseline to Week 12 in FSFI Total Score as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  38. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal

    Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  39. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire

    Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  40. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication

    Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  41. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm

    Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  42. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain

    Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

  43. Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction

    Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo

    The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

    Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2014 (estimated)
  2. Study startSep 2014
  3. Primary completionOct 2015
  4. Study completionOct 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
764 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02253173
Sponsor's protocol ID
TXV14-01
Acronym
REJOICE
Status last verified
Apr 2017
First submitted
26 Sep 2014
Last updated
25 May 2017
Data monitoring committee
No

Publications

  • Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva ACJ, Ferriani RA, Martins WP, Fuentealba-Torres M. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2023 Aug 24;8(8):CD009672. doi: 10.1002/14651858.CD009672.pub3.

    PubMed 37619252
  • Mirkin S, Simon JA, Liu JH, Archer DF, Castro PD, Graham S, Bernick B, Komm B. Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert. Menopause. 2021 May 28;28(9):998-1003. doi: 10.1097/GME.0000000000001801.

    PubMed 34054104
  • Constantine G, Millheiser LS, Kaunitz AM, Parish SJ, Graham S, Bernick B, Mirkin S. Early onset of action with a 17beta-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia. Menopause. 2019 Nov;26(11):1259-1264. doi: 10.1097/GME.0000000000001394.

    PubMed 31688572
  • Constantine GD, Simon JA, Pickar JH, Archer DF, Bernick B, Graham S, Mirkin S. Estradiol vaginal inserts (4 microg and 10 microg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data. Curr Med Res Opin. 2018 Dec;34(12):2131-2136. doi: 10.1080/03007995.2018.1527578. Epub 2018 Sep 28.

    PubMed 30238814
  • Constantine GD, Bouchard C, Pickar JH, Archer DF, Graham S, Bernick B, Mirkin S. Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women. J Womens Health (Larchmt). 2017 Jun;26(6):616-623. doi: 10.1089/jwh.2016.6187. Epub 2017 Mar 29.

    PubMed 28355090

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Estradiol in people with Vulvovaginal Atrophy and Menopause, run by TherapeuticsMD at 105 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 105 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Co-Primary Efficacy Endpoint - Vaginal Superficial Cells (time frame: Baseline and 12 Weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02253173, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2017.

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