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

Phase 3

Completed

Conditions: Dyspareunia
Vulvovaginal Atrophy
Menopause
Painful Intercourse

Interventions: Drug: Estradiol
Drug: Placebo

Registration Number: NCT02253173

Lead Sponsor: TherapeuticsMD

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 764

Inclusion Criteria

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
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.

Exclusion Criteria

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.
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).
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:
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)
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Estradiol 4mcg Vaginal Softgel Capsule	Estradiol	Estradiol 4mcg Vaginal Softgel Capsule
Estradiol 25mcg Vaginal Softgel Capsule	Estradiol	Estradiol 25mcg Vaginal Softgel Capsule
Placebo Vaginal Softgel Capsule	Placebo	Placebo Vaginal Softgel Capsule
Estradiol 10mcg Vaginal Softgel Capsule	Estradiol	Estradiol 10mcg Vaginal Softgel Capsule

Primary Outcome Measures

Name	Time	Method
Co-Primary Efficacy Endpoint - Vaginal pH	Baseline and 12 Weeks	• Change from Baseline to Week 12 in vaginal pH as compared to placebo
Co-Primary Efficacy Endpoint - Vaginal Superficial Cells	Baseline and 12 Weeks	• Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells	Baseline and 12 Weeks	• Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)	Baseline and Week 12	• 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

Secondary Outcome Measures

Name	Time	Method
Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)	Baseline and Week 8	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
Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Vaginal Superficial Cells	Baseline and Week 8	Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Secondary Efficacy Endpoints - Vaginal pH	Baseline and Week 8	Change from Baseline to Week 8 in vaginal pH as compared to placebo
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score	Baseline and Week 12	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.
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication	Baseline and Week 12	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.
Secondary Efficacy Endpoints- Vaginal Superficial Cells	Baseline and Week 6	Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Secondary Efficacy Endpoints - Vaginal Parabasal Cells	Baseline and Week 8	Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm	Baseline and Week 12	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.
Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal	Baseline and Week 12	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.
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction	Baseline and Week 12	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.
Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)	Baseline and Week 12	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
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire	Baseline and Week 12	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.
Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain	Baseline and Week 12	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.

Trial Locations

Locations (101): Women's Clinic of Lincoln
🇺🇸
Lincoln, Nebraska, United States
Chattanooga Medical Research
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Chattanooga, Tennessee, United States
Medical Affiliated Research Center
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Huntsville, Alabama, United States
Futura Research
🇺🇸
Norwalk, California, United States
Clinical Research Consulting
🇺🇸
Milford, Connecticut, United States
Red Rocks OB/Gyn
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Lakewood, Colorado, United States
WR-Mount Vernon Clinical Research
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Sandy Springs, Georgia, United States
South Florida Medical Research
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Aventura, Florida, United States
Ideal Clinical Research
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North Miami Beach, Florida, United States
Cactus Clinical Research
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Mesa, Arizona, United States
Wake Research Associates
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Raleigh, North Carolina, United States
Lynn Institute of the Rockies
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Colorado Springs, Colorado, United States
Manna Research Inc
🇨🇦
St-Romuald, Quebec, Canada
Women's Health Associates
🇺🇸
Atlanta, Georgia, United States
Avail Clinical Research
🇺🇸
DeLand, Florida, United States
Suffolk OB/GYN
🇺🇸
Port Jefferson, New York, United States
Healthcare Clinical Data
🇺🇸
North Miami, Florida, United States
Advanced Clinical Research
🇺🇸
Boise, Idaho, United States
Maryland Center for Sexual Health
🇺🇸
Lutherville, Maryland, United States
South Florida Wellness & Clinical Research Institute
🇺🇸
Margate, Florida, United States
Bosque Women's Care
🇺🇸
Albuquerque, New Mexico, United States
Diex Research Montreal Inc.
🇨🇦
Montreal, Quebec, Canada
Lawrence OB-GYN Clinical Research, LLC
🇺🇸
Lawrenceville, New Jersey, United States
Pinewest OB-GYN, Inc.
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High Point, North Carolina, United States
Columbus Center for Women's Health Research
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Columbus, Ohio, United States
Clinique RSF Inc.
🇨🇦
Quebec, Canada
Columbia University Medical Center
🇺🇸
New York, New York, United States
Tidewater Clinical Research
🇺🇸
Virginia Beach, Virginia, United States
National Clinical Research-Richmond, Inc
🇺🇸
Richmond, Virginia, United States
Rapid Medical Research
🇺🇸
Cleveland, Ohio, United States
Hwca, Pllc
🇺🇸
Houston, Texas, United States
Seattle Women's Health, Research, and Gynecology
🇺🇸
Seattle, Washington, 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
New Age Medical Research Corporation
🇺🇸
Miami, Florida, United States
Office of Edmond E. Pack, MD
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Las Vegas, Nevada, United States
Office of R. Garn Mabey, MD
🇺🇸
Las Vegas, Nevada, United States
University of Cincinnati Physicians Company
🇺🇸
Cincinnati, Ohio, United States
Women's Wellness Clinic
🇺🇸
Durham, North Carolina, United States
Stone Oak, LLC dba Discovery Clinical Trials
🇺🇸
San Antonio, Texas, United States
Cypress Medical Research Center
🇺🇸
Wichita, Kansas, United States
Arizona Wellness Center for Women
🇺🇸
Phoenix, Arizona, United States
Downtown Women's Health Care
🇺🇸
Denver, Colorado, United States
Horizons Clinical Research Center
🇺🇸
Denver, Colorado, United States
Montogomery Women's Health
🇺🇸
Montgomery, Alabama, United States
Visions Clinical Research - Tucson
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Tucson, Arizona, United States
Sutter East Bay Medical Foundation
🇺🇸
Berkeley, California, United States
Torrance Clinical Research Institute Inc
🇺🇸
Lomita, California, United States
Northern California Research
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Sacramento, California, United States
Coastal Connecticut Research, LLC
🇺🇸
New London, Connecticut, United States
James A. Simon, Women's Health & Research Consultants
🇺🇸
Washington, D.C., District of Columbia, United States
UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology
🇺🇸
Jacksonville, Florida, United States
UF Health Physicians Women's & REI Springhill
🇺🇸
Gainesville, Florida, United States
Clinical Physiology Associates
🇺🇸
Fort Myers, Florida, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
Suncoast Clinical Research, Inc.
🇺🇸
New Port Richey, Florida, United States
All Women's Healthcare of West Broward
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Plantation, Florida, United States
Physician Care Clinical Research
🇺🇸
Sarasota, Florida, United States
Masters of Clinical Research, Inc.
🇺🇸
Augusta, Georgia, United States
American Health Network of Indiana, LLC
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Avon, Indiana, United States
Fellows Research Alliance, Inc.
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Bluffton, South Carolina, United States
Capital Women's Care
🇺🇸
Frederick, Maryland, United States
ClinSite, LLC
🇺🇸
Ann Arbor, Michigan, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸
New Brunswick, New Jersey, United States
Lillestol Research
🇺🇸
Fargo, North Dakota, United States
The Clinical Trial Center
🇺🇸
Jenkintown, Pennsylvania, United States
Clinical Trials Research Services
🇺🇸
Pittsburgh, Pennsylvania, United States
Coastal Carolina Research Center
🇺🇸
Mount Pleasant, South Carolina, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Clinical Research Center, EVMS
🇺🇸
Norfolk, Virginia, United States
National Clinical Research-Norfolk
🇺🇸
Norfolk, Virginia, United States
Virginia Women's Center, Inc.
🇺🇸
Richmond, Virginia, United States
Diex Research Sherbrooke Inc.
🇨🇦
Sherbrooke, Quebec, Canada
Horizon Research Group of Opelousas
🇺🇸
Eunice, Louisiana, United States
Women's Healthcare Associates P.A.
🇺🇸
Idaho Falls, Idaho, United States
Vista Clinical Research
🇺🇸
Columbia, South Carolina, United States
Montana Health
🇺🇸
Billings, Montana, United States
Women's Health Research Center
🇺🇸
Plainsboro, New Jersey, United States
Center for Research Saint-Louis
🇨🇦
Quebec, Canada
Hawthorne Research
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Winston-Salem, North Carolina, United States
Nature Coast Clinical Research
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Crystal River, Florida, United States
Comprehensive Clinical Trials
🇺🇸
West Palm Beach, Florida, United States
Lafayette Clinical Research Group
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Lafayette, Indiana, United States
Soapstone Center for Clinical Research
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Decatur, Georgia, United States
Bluegrass Clinical Research, Inc.
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Louisville, Kentucky, United States
Beyer Research
🇺🇸
Kalamazoo, Michigan, United States
Southwest Clinical Research
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Albuquerque, New Mexico, United States
HWC Women's Research Center
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Englewood, Ohio, United States
Clinical Research of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
North Spokane Women's Health
🇺🇸
Spokane, Washington, United States
Landerbrook Health Center
🇺🇸
Mayfield Heights, Ohio, United States
Sunstone Medical Research
🇺🇸
Medford, Oregon, United States
Advanced Research Associates
🇺🇸
Corpus Christi, Texas, United States
TMC Life Research
🇺🇸
Houston, Texas, United States
Central Kentucky Research Associates, Inc.
🇺🇸
Lexington, Kentucky, United States
Lyndhurst Clinical Research
🇺🇸
Winston-Salem, North Carolina, United States
Research Across America
🇺🇸
Dallas, Texas, United States
Saginaw Valley Medical Research Group, L.L.C.
🇺🇸
Saginaw, Michigan, United States
Advances in Health
🇺🇸
Houston, Texas, United States
Radiant Research
🇺🇸
Akron, Ohio, United States