A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis

NCT ID: NCT02195986

Last Updated: 2022-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 366 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2014-12-31

Brief Summary

The purpose of this study is to determine the therapeutic equivalence of Mylan's estradiol vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7 day treatment.

Conditions

Atrophic Vaginitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Estradiol Vaginal Cream

Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.

Group Type: EXPERIMENTAL

Estradiol Vaginal Cream, 0.01%

Intervention Type: DRUG

Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)

Estrace® 0.01% cream

Estrace® 0.01% vaginal cream, administered once daily for 7 days.

Group Type: ACTIVE_COMPARATOR

Estrace® 0.01% cream

Intervention Type: DRUG

Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)

Placebo Vaginal Cream

Placebo Vaginal Cream, administered once daily for 7 days.

Group Type: PLACEBO_COMPARATOR

Placebo Vaginal Cream

Intervention Type: DRUG

Placebo Vaginal Cream ( 1 x 2 g for 7 days)

Interventions

Estradiol Vaginal Cream, 0.01%

Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)

Intervention Type: DRUG

Estrace® 0.01% cream

Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)

Intervention Type: DRUG

Placebo Vaginal Cream

Placebo Vaginal Cream ( 1 x 2 g for 7 days)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Capable of providing informed consent.

2. Age: 40-70 years old.

3. Sex: Female

4. Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.

5. Weight: At least 48 kg with all subjects having a Body Mass Index less than or equal to 38 kg/m2 but greater than or equal to 19 kg/m2.

6. Baseline evaluation requirements:

• ≤5% superficial cells on vaginal smear cytology
• Vaginal pH > 5.0
• At least one patient self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy (VVA) from the following list that is identified by the subject:
• Vaginal dryness
• Vaginal and/or vulvar irritation/itching
• Dysuria
• Vaginal pain associated with sexual activity
• Vaginal bleeding associated with sexual activity (absence vs. presence)

7. All subjects should be judged to be eligible for participation in this study by the principal or sub-investigator physician during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:

1. a normal or non-clinically significant physical examination, including vital signs

2. a normal or non-clinically significant pelvic examination that was consistent with hypoestrogenemia

3. a normal or non-clinically significant breast exam and mammogram

4. a normal or non-clinically significant ASCUS Papanicolaou ("Pap") smear that is negative for HPV for subjects with an intact uterus and cervix

Exclusion Criteria

• Serum Chemistry
• Hematology
• Coagulogram
• Urinalysis

6. normal or non-clinically significant 12- Lead ECG.

8. negative urine cotinine test.

8. For women with an intact uterus, an endometrial thickness < 5 mm as determined by vaginal ultrasonography.

9. If warranted, other tests or examinations may be performed at the discretion of the Principal Investigator or responsible physician.

10. Ability to use applicator properly.

1. Institutionalized subjects will not be used.

2. Any contraindication to estrogen therapy.

3. Social Habits:

1. Use of any tobacco-containing products within 1 year of the start of the study.

2. Regular intake of more than 7 units of alcohol per week.

3. Beginning any new regimens of vitamins or herbal products within 7 days prior to the initial dose of the study medication.

4. Any recent, significant change in dietary or exercise habits.

5. History of drug and/or alcohol abuse within one year of start of study.

4. Medications:

2. Use of hormonal replacement therapies for the following time periods:

• within 2 weeks of baseline assessment for vaginal therapy (rings, creams, gels)
• within 4 weeks of baseline assessment for transdermal estrogen alone or estrogen/progestin therapy
• within 8 weeks of baseline assessment for oral estrogen and/or progestin therapy or intrauterine progestin therapy
• within 3 months of baseline assessments for progestin implants or estrogen alone injectable therapy
• within 6 months of baseline assessments for estrogen pellet or progestin injectable therapy

3. A depot injection or implant of any drug within 3 months prior to administration of study medication.

4. Currently taking medication indicated for anticoagulation as a result of an excluded condition listed in #5 below. This includes but is not limited to warfarin, heparin, NSAIDs, clopidogrel, dabigatran, etc.

5. Diseases:

1. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, urinary, musculoskeletal disease or malignancies unless under medical control and/or deemed not clinically significant by the Principal Investigator or Medical Sub-investigator.

2. Manifestation or treatment for significant cardiovascular disease (congestive heart failure, stroke or ischemic attack, myocardial infarction, coronary artery bypass, percutaneous angioplasty or > 50% angiographic narrowing of coronary artery, thrombosis of deep veins and arteries, thromboembolic disorders, pulmonary embolism) or history of these conditions.

3. Coronary artery or cerebrovascular disease.

4. Current clinically significant liver or kidney dysfunction/disorders.

5. Current clinically significant gallbladder dysfunction/disorders.

6. Abnormal or clinically significant breast examination. Acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.

7. First degree family history of breast cancer.

8. Current non diet controlled diabetes mellitus or other clinically significant endocrinological disease.

9. Estrogen-dependent neoplasia

10. Postmenopausal uterine bleeding

11. Endometrial hyperplasia

12. Uncontrolled hypothyroidism

13. Urinalysis showing an ongoing clinically significant urinary tract infection that requires treatment.

14. Current clinically significant vaginal infection that requires treatment.

15. Known chronic lichen sclerosis

16. Acute illness at the time of either the pre-study medical evaluation or dosing.

17. History of allergy or hypersensitivity to estradiol, other related products, or any inactive ingredients.

18. Undiagnosed vaginal bleeding or history of significant risk factors for endometrial cancer.

19. Increased frequency or severity of headaches while on previous hormone or estrogen therapy.

20. History of psychiatric disorders occurring within the last 6 months that require hospitalization or medication.

21. Current hypercalcemia, hypocalcemia, and/or hypertriglyceridemia.

22. Clinically significant eye/visual abnormalities such as retinal vascular thrombosis, partial or complete loss of vision, proptosis, diplopia, papilledema, retinal vascular lesions.

6. Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study.

7. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.

8. Sitting blood pressure higher than 150/90 mmHg at screening.

9. Baseline serum estradiol levels >30 pg/mL at screening.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Mylan Pharmaceuticals Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matt Hummel, Ph.D.

Role: STUDY_CHAIR

Mylan Pharmaceuticals Inc

Ronald Ackerman, M.D.

Role: PRINCIPAL_INVESTIGATOR

Comprehensive Clinical Trials, LLC

James Andersen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Meridien Research

Keith Aqua, M.D.

Role: PRINCIPAL_INVESTIGATOR

Visions Clinical Research

Theodore Cooper, M.D.

Role: PRINCIPAL_INVESTIGATOR

Horizons Clinical Research Center, LLC

Scott Eder, M.D.

Role: PRINCIPAL_INVESTIGATOR

Women's Health Research Center/The Center for Women's Health & Wellness, LLC

William Koltun, M.D.

Role: PRINCIPAL_INVESTIGATOR

Medical Center for Clinical Research

Gigi Lefebvre, M.D.

Role: PRINCIPAL_INVESTIGATOR

Meridien Research

Leonard Ranasinghe, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northern CA Research

Rovena Reagan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Women's Health Care Research Corp.

Ronald Surowitz, D.O.

Role: PRINCIPAL_INVESTIGATOR

Health Awareness, Inc.

Steven Sussman, M.D.

Role: PRINCIPAL_INVESTIGATOR

Lawrence OB/GYN Clinical Research, LLC

G. Michael Swor, M.D.

Role: PRINCIPAL_INVESTIGATOR

Physician Care Clinical Research LLC

Olga Tudela, M.D.

Role: PRINCIPAL_INVESTIGATOR

Veritas Research., Corp.

Arthur Waldbaum, M.D.

Role: PRINCIPAL_INVESTIGATOR

Downtown Women's Health Care

Maria C Fernandez, M.D.

Role: PRINCIPAL_INVESTIGATOR

South Coast Research Center, Inc.

Gary Carson, M.D

Role: PRINCIPAL_INVESTIGATOR

Northern CA Research

Lydie Hazan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Axis Clinical Trials

Alfred Moffett, M.D.

Role: PRINCIPAL_INVESTIGATOR

OB-GYN Associates of Mid Florida

Tracey Lemon, M.D.

Role: PRINCIPAL_INVESTIGATOR

Georgia Center for Women

Steven Foley, M.D.

Role: PRINCIPAL_INVESTIGATOR

MCB Clinical Research Centers, LLC

Jason Haffizulla, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sunrise Medical Research, Inc.

Robert Hunter, M.D.

Role: PRINCIPAL_INVESTIGATOR

ARA-Arizona Research Associates

Locations

ARA-Arizona Research Associates

Tucson, Arizona, United States

Axis Clinical Trials

Los Angeles, California, United States

Northern CA Research

Sacramento, California, United States

MCCR

San Diego, California, United States

Women's Health Care Research Corp.

San Diego, California, United States

MCB Clinical Research Centers

Colorado Springs, Colorado, United States

Downtown Women's Health Care

Denver, Colorado, United States

Horizons Clinical Research Center, LLC

Denver, Colorado, United States

Sunrise Medical Research

Coral Springs, Florida, United States

Health Awareness, Inc.

Jupiter, Florida, United States

Meridien Research

Lakeland, Florida, United States

OB-GYN Associates of Mid Florida

Leesburg, Florida, United States

SouthCoast Research Center

Miami, Florida, United States

Veritas Research, Corp.

Miami Lakes, Florida, United States

Physician Care Clinical Research LLC

Sarasota, Florida, United States

Meridien Research

St. Petersburg, Florida, United States

Sunrise Medical Research

Tamarac, Florida, United States

Comprehensive Clinical Trials, LLC

West Palm Beach, Florida, United States

Georgia Center for Women

Atlanta, Georgia, United States

Lawrence OB/GYN Clinical Research, LLC

Lawrenceville, New Jersey, United States

Women's Health Research Center/The Center for Women's Health & Wellness, LLC

Plainsboro, New Jersey, United States

Countries

United States

Other Identifiers

EVCR-11196

Identifier Type: -

Identifier Source: org_study_id