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Trial record 37 of 2076 for:    ESTRADIOL

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

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ClinicalTrials.gov Identifier: NCT02195986
Recruitment Status : Completed
First Posted : July 21, 2014
Results First Posted : September 6, 2017
Last Update Posted : November 29, 2017
Sponsor:
Collaborator:
Mylan Pharmaceuticals
Information provided by (Responsible Party):
Mylan Inc.

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.

Condition or disease Intervention/treatment Phase
Atrophic Vaginitis Drug: Estradiol Vaginal Cream, 0.01% Drug: Estrace® 0.01% cream Drug: Placebo Vaginal Cream Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 366 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Endpoint Therapeutic Equivalence Multi-Site Study Comparing Estradiol Vaginal Cream (0.01%; Mylan) to Estrace® Cream (0.01%; Warner Chilcott) in Postmenopausal Females With Atrophic Vaginitis
Study Start Date : June 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaginitis

Arm Intervention/treatment
Experimental: Estradiol Vaginal Cream
Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.
Drug: Estradiol Vaginal Cream, 0.01%
Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)

Active Comparator: Estrace® 0.01% cream
Estrace® 0.01% vaginal cream, administered once daily for 7 days.
Drug: Estrace® 0.01% cream
Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)

Placebo Comparator: Placebo Vaginal Cream
Placebo Vaginal Cream, administered once daily for 7 days.
Drug: Placebo Vaginal Cream
Placebo Vaginal Cream ( 1 x 2 g for 7 days)




Primary Outcome Measures :
  1. Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence [ Time Frame: Study Day 8 ]

    Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream or Estrace® that were identified as responders at the end of the treatment period on Study Day 8.

    A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.


  2. Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo [ Time Frame: Study Day 8 ]

    Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream, Estrace®, or Placebo that were identified as responders at the end of the treatment period on Study Day 8.

    A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.



Secondary Outcome Measures :
  1. Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence [ Time Frame: Day 8 ]
    Evaluation and comparison between Estradiol Vaginal Cream and Estrace® treatment groups of the change from baseline in the most bothersome vulvar and/or vaginal atrophy symptom including vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, or vaginal bleeding associated with sexual activity as identified by each subject. A score ≤ 1 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment success. A score ≥ 2 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment failure.

  2. Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Comparison to Placebo [ Time Frame: Day 8 ]
    Evaluation and comparison between Estradiol Vaginal Cream, Estrace®, and Placebo treatment groups of the change from baseline in the most bothersome vulvar and/or vaginal atrophy symptom including vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, or vaginal bleeding associated with sexual activity as identified by each subject. A score ≤ 1 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment success. A score ≥ 2 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment failure.



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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
    5. within normal limits or non-clinically significant laboratory evaluation results (unless otherwise noted in the exclusion criteria) for the following tests:

      • Serum Chemistry
      • Hematology
      • Coagulogram
      • Urinalysis
    6. normal or non-clinically significant 12- Lead ECG.
    7. negative urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, methadone and phencyclidine with the following exceptions: positive tests for amphetamines, barbiturates, benzodiazepines, or opiates may be allowed provided the subject has a valid prescription and is on a stable regimen that complies with Exclusion Criteria, Section 6.3.2.
    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.

Exclusion Criteria:

  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:

    1. Use of any new prescription or over-the-counter (OTC) medication regimens within fourteen (14) days prior to the initial dose of study medication (any necessary medication, unless otherwise noted in the exclusion criteria, for which dosing has been stabilized for a period of at least 14 days prior to initial dosing of study drug and is expected to remain stable for the entire study period is allowed, with the exception of acetaminophen, which may be administered as needed to treat minor adverse events).
    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02195986


Locations
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United States, Arizona
ARA-Arizona Research Associates
Tucson, Arizona, United States, 85712
United States, California
Axis Clinical Trials
Los Angeles, California, United States, 90036
Northern CA Research
Sacramento, California, United States, 95821
MCCR
San Diego, California, United States, 92108
Women's Health Care Research Corp.
San Diego, California, United States, 92123
United States, Colorado
MCB Clinical Research Centers
Colorado Springs, Colorado, United States, 80910
Downtown Women's Health Care
Denver, Colorado, United States, 80209
Horizons Clinical Research Center, LLC
Denver, Colorado, United States, 80220
United States, Florida
Sunrise Medical Research
Coral Springs, Florida, United States, 33065
Health Awareness, Inc.
Jupiter, Florida, United States, 33458
Meridien Research
Lakeland, Florida, United States, 33805
OB-GYN Associates of Mid Florida
Leesburg, Florida, United States, 34748
Veritas Research, Corp.
Miami Lakes, Florida, United States, 33014
SouthCoast Research Center
Miami, Florida, United States, 33136
Meridien Research
Saint Petersburg, Florida, United States, 33709
Physician Care Clinical Research LLC
Sarasota, Florida, United States, 34239
Sunrise Medical Research
Tamarac, Florida, United States, 33351
Comprehensive Clinical Trials, LLC
West Palm Beach, Florida, United States, 33409
United States, Georgia
Georgia Center for Women
Atlanta, Georgia, United States, 30312
United States, New Jersey
Lawrence OB/GYN Clinical Research, LLC
Lawrenceville, New Jersey, United States, 08690
Women's Health Research Center/The Center for Women's Health & Wellness, LLC
Plainsboro, New Jersey, United States, 08536
Sponsors and Collaborators
Mylan Inc.
Mylan Pharmaceuticals
Investigators
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Study Chair: Matt Hummel, Ph.D. Mylan Pharmaceuticals
Principal Investigator: Ronald Ackerman, M.D. Comprehensive Clinical Trials, LLC
Principal Investigator: James Andersen, M.D. Meridien Research
Principal Investigator: Keith Aqua, M.D. Visions Clinical Research
Principal Investigator: Theodore Cooper, M.D. Horizons Clinical Research Center, LLC
Principal Investigator: Scott Eder, M.D. Women's Health Research Center/The Center for Women's Health & Wellness, LLC
Principal Investigator: William Koltun, M.D. Medical Center for Clinical Research
Principal Investigator: Gigi Lefebvre, M.D. Meridien Research
Principal Investigator: Leonard Ranasinghe, M.D. Northern CA Research
Principal Investigator: Rovena Reagan, M.D. Women's Health Care Research Corp.
Principal Investigator: Ronald Surowitz, D.O. Health Awareness, Inc.
Principal Investigator: Steven Sussman, M.D. Lawrence OB/GYN Clinical Research, LLC
Principal Investigator: G. Michael Swor, M.D. Physician Care Clinical Research LLC
Principal Investigator: Olga Tudela, M.D. Veritas Research., Corp.
Principal Investigator: Arthur Waldbaum, M.D. Downtown Women's Health Care
Principal Investigator: Maria C Fernandez, M.D. South Coast Research Center, Inc.
Principal Investigator: Gary Carson, M.D Northern CA Research
Principal Investigator: Lydie Hazan, M.D. Axis Clinical Trials
Principal Investigator: Alfred Moffett, M.D. OB-GYN Associates of Mid Florida
Principal Investigator: Tracey Lemon, M.D. Georgia Center for Women
Principal Investigator: Steven Foley, M.D. MCB Clinical Research Centers, LLC
Principal Investigator: Jason Haffizulla, M.D. Sunrise Medical Research, Inc.
Principal Investigator: Robert Hunter, M.D. ARA-Arizona Research Associates

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Responsible Party: Mylan Inc.
ClinicalTrials.gov Identifier: NCT02195986     History of Changes
Other Study ID Numbers: EVCR-11196
First Posted: July 21, 2014    Key Record Dates
Results First Posted: September 6, 2017
Last Update Posted: November 29, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: N/A - Phase I study
Keywords provided by Mylan Inc.:
vaginal dryness
vaginal and/or vulvar irritation/itching
dysuria
vaginal pain and bleeding associated with sexual activity
vaginal atrophy
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Vaginitis
Atrophic Vaginitis
Atrophy
Pathological Conditions, Anatomical
Vaginal Diseases
Genital Diseases, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female