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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.

Tracking Information
First Submitted Date  ICMJE July 16, 2014
First Posted Date  ICMJE July 21, 2014
Results First Submitted Date  ICMJE August 4, 2017
Results First Posted Date  ICMJE September 6, 2017
Last Update Posted Date November 29, 2017
Study Start Date  ICMJE June 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2014)
  • Vaginal Cytology [ Time Frame: Study Day 8 ]
    Proportion of patients in the Per Protocol (PP) population that are identified as responders at the end of the treatment period on Study Day 8. A responder is defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology.
  • Vaginal pH [ Time Frame: Study Day 8 ]
    Vaginal pH <5.0 with change from baseline vaginal pH of at least 0.5.
Change History Complete list of historical versions of study NCT02195986 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2014)
Patient self-assessment of the symptoms of vulvar and vaginal atrophy [ Time Frame: Day 8 ]
Evaluation and comparison between 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) will be 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) will be considered a treatment failure.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Atrophic Vaginitis
Intervention  ICMJE
  • Drug: Estradiol Vaginal Cream, 0.01%
    Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)
  • Drug: Estrace® 0.01% cream
    Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)
  • Drug: Placebo Vaginal Cream
    Placebo Vaginal Cream ( 1 x 2 g for 7 days)
Study Arms  ICMJE
  • Experimental: Estradiol Vaginal Cream
    Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.
    Intervention: Drug: Estradiol Vaginal Cream, 0.01%
  • Active Comparator: Estrace® 0.01% cream
    Estrace® 0.01% vaginal cream, administered once daily for 7 days.
    Intervention: Drug: Estrace® 0.01% cream
  • Placebo Comparator: Placebo Vaginal Cream
    Placebo Vaginal Cream, administered once daily for 7 days.
    Intervention: Drug: Placebo Vaginal Cream
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 9, 2015)
366
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2014)
350
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 40 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02195986
Other Study ID Numbers  ICMJE EVCR-11196
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: N/A - Phase I study
Responsible Party Mylan Inc.
Study Sponsor  ICMJE Mylan Inc.
Collaborators  ICMJE Mylan Pharmaceuticals
Investigators  ICMJE
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
PRS Account Mylan Inc.
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP