Estradiol Vaginal Softgel Capsules in Treating Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women
REJOICE
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
1 other identifier
interventional
764
2 countries
105
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2014
Shorter than P25 for phase_3
105 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2014
CompletedFirst Submitted
Initial submission to the registry
September 26, 2014
CompletedFirst Posted
Study publicly available on registry
October 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedResults Posted
Study results publicly available
May 25, 2017
CompletedMay 25, 2017
April 1, 2017
1.1 years
September 26, 2014
August 8, 2016
April 20, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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
Baseline and 12 Weeks
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
Baseline and 12 Weeks
Co-Primary Efficacy Endpoint - Vaginal pH
• Change from Baseline to Week 12 in vaginal pH as compared to placebo
Baseline and 12 Weeks
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
Baseline and Week 12
Secondary Outcomes (43)
Secondary Efficacy Endpoints - Vaginal Superficial Cells
Baseline and Week 2
Secondary Efficacy Endpoints- Vaginal Superficial Cells
Baseline and Week 6
Secondary Efficacy Endpoints - Vaginal Superficial Cells
Baseline and Week 8
Secondary Efficacy Endpoints - Vaginal Parabasal Cells
Baseline and Week 2
Secondary Efficacy Endpoints - Vaginal Parabasal Cells
Baseline and Week 6
- +38 more secondary outcomes
Other Outcomes (1)
PK Substudy - Hormone Concentration Assessments (Serum Estradiol, Estrone and Estrone Conjugates; SHBG)
Pre-treatment, Day 2, Weeks 2 and 12
Study Arms (4)
Estradiol 4mcg Vaginal Softgel Capsule
EXPERIMENTALEstradiol 4mcg Vaginal Softgel Capsule
Estradiol 10mcg Vaginal Softgel Capsule
EXPERIMENTALEstradiol 10mcg Vaginal Softgel Capsule
Estradiol 25mcg Vaginal Softgel Capsule
EXPERIMENTALEstradiol 25mcg Vaginal Softgel Capsule
Placebo Vaginal Softgel Capsule
PLACEBO COMPARATORPlacebo Vaginal Softgel Capsule
Interventions
Eligibility Criteria
You may qualify if:
- Postmenopausal female subjects between the ages of 40 and 75 years (at the time of randomization) with at least:
- 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
- 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
- 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.
You may not qualify if:
- 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);
- 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;
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- TherapeuticsMDlead
Study Sites (105)
Medical Affiliated Research Center
Huntsville, Alabama, 35801, United States
Montogomery Women's Health
Montgomery, Alabama, 36117, United States
Cactus Clinical Research
Mesa, Arizona, 85209, United States
Arizona Wellness Center for Women
Phoenix, Arizona, 85032, United States
Radiant Research
Scottsdale, Arizona, 85251, United States
Visions Clinical Research - Tucson
Tucson, Arizona, 85712, United States
Sutter East Bay Medical Foundation
Berkeley, California, 94705, United States
Torrance Clinical Research Institute Inc
Lomita, California, 90717, United States
Futura Research
Norwalk, California, 90650, United States
Northern California Research
Sacramento, California, 95821, United States
Medical Center for Clinical Research
San Diego, California, 92108, United States
San Diego Sexual Medicine
San Diego, California, 92120, United States
Women's Health Care Research Corp.
San Diego, California, 92123, United States
Lynn Institute of the Rockies
Colorado Springs, Colorado, 80909, United States
Downtown Women's Health Care
Denver, Colorado, 80209, United States
Horizons Clinical Research Center
Denver, Colorado, 80220, United States
Red Rocks OB/Gyn
Lakewood, Colorado, 80228, United States
Clinical Research Consulting
Milford, Connecticut, 06460, United States
Coastal Connecticut Research, LLC
New London, Connecticut, 06320, United States
James A. Simon, Women's Health & Research Consultants
Washington D.C., District of Columbia, 20036, United States
South Florida Medical Research
Aventura, Florida, 33180, United States
Nature Coast Clinical Research
Crystal River, Florida, 34429, United States
Avail Clinical Research
DeLand, Florida, 32720, United States
Clinical Physiology Associates
Fort Myers, Florida, 33916, United States
UF Health Physicians Women's & REI Springhill
Gainesville, Florida, 32606, United States
UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology
Jacksonville, Florida, 32207, United States
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216, United States
South Florida Wellness & Clinical Research Institute
Margate, Florida, 33063, United States
New Age Medical Research Corporation
Miami, Florida, 33186, United States
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652, United States
Healthcare Clinical Data
North Miami, Florida, 33161, United States
Ideal Clinical Research
North Miami Beach, Florida, 33162, United States
Radiant Research
Pinellas Park, Florida, 33781, United States
All Women's Healthcare of West Broward
Plantation, Florida, 33324, United States
Physician Care Clinical Research
Sarasota, Florida, 34239, United States
Comprehensive Clinical Trials
West Palm Beach, Florida, 33409, United States
Women's Health Associates
Atlanta, Georgia, 30342, United States
Masters of Clinical Research, Inc.
Augusta, Georgia, 30909, United States
Soapstone Center for Clinical Research
Decatur, Georgia, 30034, United States
WR-Mount Vernon Clinical Research
Sandy Springs, Georgia, 30328, United States
Fellows Research Alliance, Inc.
Savannah, Georgia, 31046, United States
Advanced Clinical Research
Boise, Idaho, 83642, United States
Women's Healthcare Associates P.A.
Idaho Falls, Idaho, 83404, United States
Radiant Research
Chicago, Illinois, 60654, United States
American Health Network of Indiana, LLC
Avon, Indiana, 46123, United States
Lafayette Clinical Research Group
Lafayette, Indiana, 47905, United States
Cypress Medical Research Center
Wichita, Kansas, 67226, United States
Central Kentucky Research Associates, Inc.
Lexington, Kentucky, 40509, United States
Bluegrass Clinical Research, Inc.
Louisville, Kentucky, 40291, United States
Horizon Research Group of Opelousas
Eunice, Louisiana, 70535, United States
Capital Women's Care
Frederick, Maryland, 21702, United States
Maryland Center for Sexual Health
Lutherville, Maryland, 21093, United States
ClinSite, LLC
Ann Arbor, Michigan, 48106, United States
Beyer Research
Kalamazoo, Michigan, 49009, United States
Saginaw Valley Medical Research Group, L.L.C.
Saginaw, Michigan, 48604, United States
Montana Health
Billings, Montana, 59102, United States
Women's Clinic of Lincoln
Lincoln, Nebraska, 68510, United States
Office of Edmond E. Pack, MD
Las Vegas, Nevada, 89113, United States
Office of R. Garn Mabey, MD
Las Vegas, Nevada, 89128, United States
Lawrence OB-GYN Clinical Research, LLC
Lawrenceville, New Jersey, 08648, United States
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901, United States
Women's Health Research Center
Plainsboro, New Jersey, 08536, United States
Bosque Women's Care
Albuquerque, New Mexico, 87109, United States
Southwest Clinical Research
Albuquerque, New Mexico, 87109, United States
Columbia University Medical Center
New York, New York, 10032, United States
Suffolk OB/GYN
Port Jefferson, New York, 08536, United States
Women's Wellness Clinic
Durham, North Carolina, 27713, United States
Pinewest OB-GYN, Inc.
High Point, North Carolina, 27262, United States
Wake Research Associates
Raleigh, North Carolina, 27612, United States
Hawthorne Research
Winston-Salem, North Carolina, 27103, United States
Lyndhurst Clinical Research
Winston-Salem, North Carolina, 27103, United States
Lillestol Research
Fargo, North Dakota, 58103, United States
Radiant Research
Akron, Ohio, 44311, United States
University of Cincinnati Physicians Company
Cincinnati, Ohio, 45267-0457, United States
Rapid Medical Research
Cleveland, Ohio, 44122, United States
Columbus Center for Women's Health Research
Columbus, Ohio, 43213, United States
HWC Women's Research Center
Englewood, Ohio, 45322, United States
Landerbrook Health Center
Mayfield Heights, Ohio, 44124, United States
Sunstone Medical Research
Medford, Oregon, 97504, United States
The Clinical Trial Center
Jenkintown, Pennsylvania, 19046, United States
Clinical Research of Philadelphia
Philadelphia, Pennsylvania, 19114, United States
Clinical Trials Research Services
Pittsburgh, Pennsylvania, 15206, United States
Fellows Research Alliance, Inc.
Bluffton, South Carolina, 29910, United States
Vista Clinical Research
Columbia, South Carolina, 29201, United States
Coastal Carolina Research Center
Mt. Pleasant, South Carolina, 29464, United States
Chattanooga Medical Research
Chattanooga, Tennessee, 37404, United States
Advanced Research Associates
Corpus Christi, Texas, 78414, United States
Research Across America
Dallas, Texas, 75234, United States
UT Southwestern Medical Center
Dallas, Texas, 75390-9032, United States
Advances in Health
Houston, Texas, 77030, United States
Hwca, Pllc
Houston, Texas, 77054, United States
TMC Life Research
Houston, Texas, 77054, United States
Stone Oak, LLC dba Discovery Clinical Trials
San Antonio, Texas, 78258, United States
National Clinical Research-Norfolk
Norfolk, Virginia, 23502, United States
Clinical Research Center, EVMS
Norfolk, Virginia, 23507, United States
Virginia Women's Center, Inc.
Richmond, Virginia, 23233, United States
National Clinical Research-Richmond, Inc
Richmond, Virginia, 23294, United States
Tidewater Clinical Research
Virginia Beach, Virginia, 23456, United States
Seattle Women's Health, Research, and Gynecology
Seattle, Washington, 98105, United States
North Spokane Women's Health
Spokane, Washington, 99207, United States
Diex Research Montreal Inc.
Montreal, Quebec, H4N 3C5, Canada
Center for Research Saint-Louis
Québec, Quebec, G1W4R4, Canada
Manna Research Inc
Saint Romuald, Quebec, G6W 5M6, Canada
Diex Research Sherbrooke Inc.
Sherbrooke, Quebec, J1H 1Z1, Canada
Clinique RSF Inc.
Québec, G1S 2L6, Canada
Related Publications (5)
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.
PMID: 37619252DERIVEDMirkin 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.
PMID: 34054104DERIVEDConstantine 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.
PMID: 31688572DERIVEDConstantine 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.
PMID: 30238814DERIVEDConstantine 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.
PMID: 28355090DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sebastian Mirkin, MD, Chief Medical Officer
- Organization
- TherapeuticsMD
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2014
First Posted
October 1, 2014
Study Start
September 1, 2014
Primary Completion
October 1, 2015
Study Completion
October 1, 2015
Last Updated
May 25, 2017
Results First Posted
May 25, 2017
Record last verified: 2017-04