<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02195986</url>
  </required_header>
  <id_info>
    <org_study_id>EVCR-11196</org_study_id>
    <nct_id>NCT02195986</nct_id>
  </id_info>
  <brief_title>A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mylan Pharmaceuticals Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Viatris Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the therapeutic equivalence of Mylan's estradiol&#xD;
      vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol&#xD;
      describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7&#xD;
      day treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence</measure>
    <time_frame>Study Day 8</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo</measure>
    <time_frame>Study Day 8</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence</measure>
    <time_frame>Day 8</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Day 8</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">366</enrollment>
  <condition>Atrophic Vaginitis</condition>
  <arm_group>
    <arm_group_label>Estradiol Vaginal Cream</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Estrace® 0.01% cream</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Vaginal Cream</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Vaginal Cream, administered once daily for 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol Vaginal Cream, 0.01%</intervention_name>
    <description>Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)</description>
    <arm_group_label>Estradiol Vaginal Cream</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estrace® 0.01% cream</intervention_name>
    <description>Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)</description>
    <arm_group_label>Estrace® 0.01% cream</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Vaginal Cream</intervention_name>
    <description>Placebo Vaginal Cream ( 1 x 2 g for 7 days)</description>
    <arm_group_label>Placebo Vaginal Cream</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Capable of providing informed consent.&#xD;
&#xD;
          2. Age: 40-70 years old.&#xD;
&#xD;
          3. Sex: Female&#xD;
&#xD;
          4. Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6&#xD;
             months of spontaneous amenorrhea with serum FSH levels &gt; 40 mIU/ml or at least 6 weeks&#xD;
             postsurgical bilateral oophorectomy with or without hysterectomy.&#xD;
&#xD;
          5. Weight: At least 48 kg with all subjects having a Body Mass Index less than or equal&#xD;
             to 38 kg/m2 but greater than or equal to 19 kg/m2.&#xD;
&#xD;
          6. Baseline evaluation requirements:&#xD;
&#xD;
               -  ≤5% superficial cells on vaginal smear cytology&#xD;
&#xD;
               -  Vaginal pH &gt; 5.0&#xD;
&#xD;
               -  At least one patient self-assessed moderate to severe symptom of vulvar and/or&#xD;
                  vaginal atrophy (VVA) from the following list that is identified by the subject:&#xD;
&#xD;
               -  Vaginal dryness&#xD;
&#xD;
               -  Vaginal and/or vulvar irritation/itching&#xD;
&#xD;
               -  Dysuria&#xD;
&#xD;
               -  Vaginal pain associated with sexual activity&#xD;
&#xD;
               -  Vaginal bleeding associated with sexual activity (absence vs. presence)&#xD;
&#xD;
          7. All subjects should be judged to be eligible for participation in this study by the&#xD;
             principal or sub-investigator physician during a pre-study medical evaluation&#xD;
             performed within 28 days of the initial dose of study medication which will include:&#xD;
&#xD;
               1. a normal or non-clinically significant physical examination, including vital&#xD;
                  signs&#xD;
&#xD;
               2. a normal or non-clinically significant pelvic examination that was consistent&#xD;
                  with hypoestrogenemia&#xD;
&#xD;
               3. a normal or non-clinically significant breast exam and mammogram&#xD;
&#xD;
               4. a normal or non-clinically significant ASCUS Papanicolaou (&quot;Pap&quot;) smear that is&#xD;
                  negative for HPV for subjects with an intact uterus and cervix&#xD;
&#xD;
               5. within normal limits or non-clinically significant laboratory evaluation results&#xD;
                  (unless otherwise noted in the exclusion criteria) for the following tests:&#xD;
&#xD;
                    -  Serum Chemistry&#xD;
&#xD;
                    -  Hematology&#xD;
&#xD;
                    -  Coagulogram&#xD;
&#xD;
                    -  Urinalysis&#xD;
&#xD;
               6. normal or non-clinically significant 12- Lead ECG.&#xD;
&#xD;
               7. negative urine drug screen including amphetamine, barbiturates, benzodiazepines,&#xD;
                  cannabinoid, cocaine, opiates, methadone and phencyclidine with the following&#xD;
                  exceptions: positive tests for amphetamines, barbiturates, benzodiazepines, or&#xD;
                  opiates may be allowed provided the subject has a valid prescription and is on a&#xD;
                  stable regimen that complies with Exclusion Criteria, Section 6.3.2.&#xD;
&#xD;
               8. negative urine cotinine test.&#xD;
&#xD;
          8. For women with an intact uterus, an endometrial thickness &lt; 5 mm as determined by&#xD;
             vaginal ultrasonography.&#xD;
&#xD;
          9. If warranted, other tests or examinations may be performed at the discretion of the&#xD;
             Principal Investigator or responsible physician.&#xD;
&#xD;
         10. Ability to use applicator properly.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Institutionalized subjects will not be used.&#xD;
&#xD;
          2. Any contraindication to estrogen therapy.&#xD;
&#xD;
          3. Social Habits:&#xD;
&#xD;
               1. Use of any tobacco-containing products within 1 year of the start of the study.&#xD;
&#xD;
               2. Regular intake of more than 7 units of alcohol per week.&#xD;
&#xD;
               3. Beginning any new regimens of vitamins or herbal products within 7 days prior to&#xD;
                  the initial dose of the study medication.&#xD;
&#xD;
               4. Any recent, significant change in dietary or exercise habits.&#xD;
&#xD;
               5. History of drug and/or alcohol abuse within one year of start of study.&#xD;
&#xD;
          4. Medications:&#xD;
&#xD;
               1. Use of any new prescription or over-the-counter (OTC) medication regimens within&#xD;
                  fourteen (14) days prior to the initial dose of study medication (any necessary&#xD;
                  medication, unless otherwise noted in the exclusion criteria, for which dosing&#xD;
                  has been stabilized for a period of at least 14 days prior to initial dosing of&#xD;
                  study drug and is expected to remain stable for the entire study period is&#xD;
                  allowed, with the exception of acetaminophen, which may be administered as needed&#xD;
                  to treat minor adverse events).&#xD;
&#xD;
               2. Use of hormonal replacement therapies for the following time periods:&#xD;
&#xD;
                    -  within 2 weeks of baseline assessment for vaginal therapy (rings, creams,&#xD;
                       gels)&#xD;
&#xD;
                    -  within 4 weeks of baseline assessment for transdermal estrogen alone or&#xD;
                       estrogen/progestin therapy&#xD;
&#xD;
                    -  within 8 weeks of baseline assessment for oral estrogen and/or progestin&#xD;
                       therapy or intrauterine progestin therapy&#xD;
&#xD;
                    -  within 3 months of baseline assessments for progestin implants or estrogen&#xD;
                       alone injectable therapy&#xD;
&#xD;
                    -  within 6 months of baseline assessments for estrogen pellet or progestin&#xD;
                       injectable therapy&#xD;
&#xD;
               3. A depot injection or implant of any drug within 3 months prior to administration&#xD;
                  of study medication.&#xD;
&#xD;
               4. Currently taking medication indicated for anticoagulation as a result of an&#xD;
                  excluded condition listed in #5 below. This includes but is not limited to&#xD;
                  warfarin, heparin, NSAIDs, clopidogrel, dabigatran, etc.&#xD;
&#xD;
          5. Diseases:&#xD;
&#xD;
               1. History of any significant cardiovascular, hepatic, renal, pulmonary,&#xD;
                  hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic,&#xD;
                  psychological, urinary, musculoskeletal disease or malignancies unless under&#xD;
                  medical control and/or deemed not clinically significant by the Principal&#xD;
                  Investigator or Medical Sub-investigator.&#xD;
&#xD;
               2. Manifestation or treatment for significant cardiovascular disease (congestive&#xD;
                  heart failure, stroke or ischemic attack, myocardial infarction, coronary artery&#xD;
                  bypass, percutaneous angioplasty or &gt; 50% angiographic narrowing of coronary&#xD;
                  artery, thrombosis of deep veins and arteries, thromboembolic disorders,&#xD;
                  pulmonary embolism) or history of these conditions.&#xD;
&#xD;
               3. Coronary artery or cerebrovascular disease.&#xD;
&#xD;
               4. Current clinically significant liver or kidney dysfunction/disorders.&#xD;
&#xD;
               5. Current clinically significant gallbladder dysfunction/disorders.&#xD;
&#xD;
               6. Abnormal or clinically significant breast examination. Acceptable breast&#xD;
                  examination is defined as no masses or other findings identified that are&#xD;
                  suspicious of malignancy.&#xD;
&#xD;
               7. First degree family history of breast cancer.&#xD;
&#xD;
               8. Current non diet controlled diabetes mellitus or other clinically significant&#xD;
                  endocrinological disease.&#xD;
&#xD;
               9. Estrogen-dependent neoplasia&#xD;
&#xD;
              10. Postmenopausal uterine bleeding&#xD;
&#xD;
              11. Endometrial hyperplasia&#xD;
&#xD;
              12. Uncontrolled hypothyroidism&#xD;
&#xD;
              13. Urinalysis showing an ongoing clinically significant urinary tract infection that&#xD;
                  requires treatment.&#xD;
&#xD;
              14. Current clinically significant vaginal infection that requires treatment.&#xD;
&#xD;
              15. Known chronic lichen sclerosis&#xD;
&#xD;
              16. Acute illness at the time of either the pre-study medical evaluation or dosing.&#xD;
&#xD;
              17. History of allergy or hypersensitivity to estradiol, other related products, or&#xD;
                  any inactive ingredients.&#xD;
&#xD;
              18. Undiagnosed vaginal bleeding or history of significant risk factors for&#xD;
                  endometrial cancer.&#xD;
&#xD;
              19. Increased frequency or severity of headaches while on previous hormone or&#xD;
                  estrogen therapy.&#xD;
&#xD;
              20. History of psychiatric disorders occurring within the last 6 months that require&#xD;
                  hospitalization or medication.&#xD;
&#xD;
              21. Current hypercalcemia, hypocalcemia, and/or hypertriglyceridemia.&#xD;
&#xD;
              22. Clinically significant eye/visual abnormalities such as retinal vascular&#xD;
                  thrombosis, partial or complete loss of vision, proptosis, diplopia, papilledema,&#xD;
                  retinal vascular lesions.&#xD;
&#xD;
          6. Any reason which, in the opinion of the Principal Investigator or Medical&#xD;
             Sub-Investigator, would prevent the subject from safely participating in the study.&#xD;
&#xD;
          7. Subjects who have received an investigational drug within 30 days prior to the initial&#xD;
             dose of study medication.&#xD;
&#xD;
          8. Sitting blood pressure higher than 150/90 mmHg at screening.&#xD;
&#xD;
          9. Baseline serum estradiol levels &gt;30 pg/mL at screening.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matt Hummel, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Mylan Pharmaceuticals Inc</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ronald Ackerman, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Comprehensive Clinical Trials, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>James Andersen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meridien Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Keith Aqua, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Visions Clinical Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Theodore Cooper, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Horizons Clinical Research Center, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Scott Eder, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Women's Health Research Center/The Center for Women's Health &amp; Wellness, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William Koltun, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical Center for Clinical Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gigi Lefebvre, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meridien Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leonard Ranasinghe, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northern CA Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rovena Reagan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Women's Health Care Research Corp.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ronald Surowitz, D.O.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Health Awareness, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Sussman, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lawrence OB/GYN Clinical Research, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>G. Michael Swor, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Physician Care Clinical Research LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Olga Tudela, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Veritas Research., Corp.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arthur Waldbaum, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Downtown Women's Health Care</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maria C Fernandez, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>South Coast Research Center, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gary Carson, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northern CA Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lydie Hazan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Axis Clinical Trials</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alfred Moffett, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>OB-GYN Associates of Mid Florida</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tracey Lemon, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgia Center for Women</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Foley, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>MCB Clinical Research Centers, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason Haffizulla, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunrise Medical Research, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Hunter, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>ARA-Arizona Research Associates</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ARA-Arizona Research Associates</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axis Clinical Trials</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern CA Research</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MCCR</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Health Care Research Corp.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MCB Clinical Research Centers</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Downtown Women's Health Care</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizons Clinical Research Center, LLC</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunrise Medical Research</name>
      <address>
        <city>Coral Springs</city>
        <state>Florida</state>
        <zip>33065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Awareness, Inc.</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Lakeland</city>
        <state>Florida</state>
        <zip>33805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OB-GYN Associates of Mid Florida</name>
      <address>
        <city>Leesburg</city>
        <state>Florida</state>
        <zip>34748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veritas Research, Corp.</name>
      <address>
        <city>Miami Lakes</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SouthCoast Research Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physician Care Clinical Research LLC</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunrise Medical Research</name>
      <address>
        <city>Tamarac</city>
        <state>Florida</state>
        <zip>33351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Clinical Trials, LLC</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Center for Women</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30312</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence OB/GYN Clinical Research, LLC</name>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <zip>08690</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Health Research Center/The Center for Women's Health &amp; Wellness, LLC</name>
      <address>
        <city>Plainsboro</city>
        <state>New Jersey</state>
        <zip>08536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>August 4, 2017</results_first_submitted>
  <results_first_submitted_qc>August 4, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">September 6, 2017</results_first_posted>
  <last_update_submitted>March 7, 2022</last_update_submitted>
  <last_update_submitted_qc>March 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vaginal dryness</keyword>
  <keyword>vaginal and/or vulvar irritation/itching</keyword>
  <keyword>dysuria</keyword>
  <keyword>vaginal pain and bleeding associated with sexual activity</keyword>
  <keyword>vaginal atrophy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaginitis</mesh_term>
    <mesh_term>Atrophic Vaginitis</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>N/A - Phase I study</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Estradiol Vaginal Cream</title>
          <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="P2">
          <title>Estrace® 0.01% Cream</title>
          <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="P3">
          <title>Placebo Vaginal Cream</title>
          <description>Placebo Vaginal Cream, administered once daily for 7 days.&#xD;
Placebo Vaginal Cream: Placebo Vaginal Cream (1 x 2 g for 7 days)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="146"/>
                <participants group_id="P2" count="147"/>
                <participants group_id="P3" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="143"/>
                <participants group_id="P2" count="142"/>
                <participants group_id="P3" count="71"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Family Emergency</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Baseline Analysis Population includes all randomized subjects.</population>
      <group_list>
        <group group_id="B1">
          <title>Estradiol Vaginal Cream</title>
          <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="B2">
          <title>Estrace® 0.01% Cream</title>
          <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="B3">
          <title>Placebo Vaginal Cream</title>
          <description>Placebo Vaginal Cream, administered once daily for 7 days.&#xD;
Placebo Vaginal Cream: Placebo Vaginal Cream (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="146"/>
            <count group_id="B2" value="147"/>
            <count group_id="B3" value="73"/>
            <count group_id="B4" value="366"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="128"/>
                    <measurement group_id="B2" value="124"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="313"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.2" spread="5.25"/>
                    <measurement group_id="B2" value="59.6" spread="5.88"/>
                    <measurement group_id="B3" value="59.4" spread="5.82"/>
                    <measurement group_id="B4" value="59.4" spread="5.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="147"/>
                    <measurement group_id="B3" value="73"/>
                    <measurement group_id="B4" value="366"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="116"/>
                    <measurement group_id="B2" value="124"/>
                    <measurement group_id="B3" value="60"/>
                    <measurement group_id="B4" value="300"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="130"/>
                    <measurement group_id="B2" value="125"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="316"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                    <measurement group_id="B2" value="147"/>
                    <measurement group_id="B3" value="73"/>
                    <measurement group_id="B4" value="366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="162.1" spread="6.43"/>
                    <measurement group_id="B2" value="161.5" spread="6.18"/>
                    <measurement group_id="B3" value="162.6" spread="6.55"/>
                    <measurement group_id="B4" value="161.9" spread="6.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.77" spread="12.74"/>
                    <measurement group_id="B2" value="69.39" spread="12.67"/>
                    <measurement group_id="B3" value="67.61" spread="11.37"/>
                    <measurement group_id="B4" value="69.19" spread="12.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.6" spread="4.41"/>
                    <measurement group_id="B2" value="26.6" spread="4.56"/>
                    <measurement group_id="B3" value="25.6" spread="4.11"/>
                    <measurement group_id="B4" value="26.4" spread="4.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence</title>
        <description>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.&#xD;
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.</description>
        <time_frame>Study Day 8</time_frame>
        <population>The Per Protocol population was used for the primary endpoint equivalence comparison which consisted of all randomized subjects that were dosed with 75%-125% of scheduled applications of Test or Reference and completed primary endpoint evaluation on Study Day 8 +/- 2 days with no protocol violations that would affect treatment evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol Vaginal Cream</title>
            <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O2">
            <title>Estrace® 0.01% Cream</title>
            <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence</title>
          <description>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.&#xD;
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.</description>
          <population>The Per Protocol population was used for the primary endpoint equivalence comparison which consisted of all randomized subjects that were dosed with 75%-125% of scheduled applications of Test or Reference and completed primary endpoint evaluation on Study Day 8 +/- 2 days with no protocol violations that would affect treatment evaluation</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The compound hypothesis to test was: H0: PT -PR &lt; -.20 or PT -PR &gt; .20 versus HA : -.20 ≤ PT -PR ≤ .20 Where PT = cure rate of test treatment, and PR = cure rate of reference treatment.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence was established for the primary endpoint if the 90% confidence interval for the difference of responder rates (test - reference) from baseline to Day 8 for the primary endpoint is contained within [-0.20, 0.20], using the per-protocol population.</non_inferiority_desc>
            <param_type>Difference</param_type>
            <param_value>-0.0062</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1209</ci_lower_limit>
            <ci_upper_limit>0.1084</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo</title>
        <description>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.&#xD;
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.</description>
        <time_frame>Study Day 8</time_frame>
        <population>The Intent-to-treat (ITT) population was used for the comparison of active treatments versus placebo analysis which consisted of all randomized subjects that used at least one dose of Test, Reference or Placebo and returned for at least one post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol Vaginal Cream</title>
            <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O2">
            <title>Estrace® 0.01% Cream</title>
            <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O3">
            <title>Placebo Vaginal Cream</title>
            <description>Placebo Vaginal Cream, administered once daily for 7 days.&#xD;
Placebo Vaginal Cream: Placebo Vaginal Cream (1 x 2 g for 7 days)</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo</title>
          <description>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.&#xD;
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.</description>
          <population>The Intent-to-treat (ITT) population was used for the comparison of active treatments versus placebo analysis which consisted of all randomized subjects that used at least one dose of Test, Reference or Placebo and returned for at least one post-baseline visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="138"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="51"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Both the test and reference products should both be statistically superior to placebo (p&lt;0.05, two-sided) using the Chi squared test with Yate's correction for the primary endpoint responder rate, using the ITT study population and last observation carried forward. The compound hypothesis to test was: H0: PT - PP ≤ 0 versus HA: PT - PP &gt; 0; Where PT = cure rate of test treatment, and PP = cure rate of placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Superiority test of test product vs placebo</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <method>Chi-squared</method>
            <param_type>Difference</param_type>
            <param_value>0.3766</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2743</ci_lower_limit>
            <ci_upper_limit>0.4790</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Both the test and reference products should both be statistically superior to placebo (p&lt;0.05, two-sided) using the Chi squared test with Yate's correction for the primary endpoint responder rate, using the ITT study population and last observation carried forward. The compound hypothesis to test was: H0: PT - PP ≤ 0 versus HA: PT - PP &gt; 0; Where PT = cure rate of test treatment, and PP = cure rate of placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Superiority test of reference product vs placebo</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <method>Chi-squared</method>
            <param_type>Difference</param_type>
            <param_value>0.3542</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2570</ci_lower_limit>
            <ci_upper_limit>0.4514</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence</title>
        <description>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.</description>
        <time_frame>Day 8</time_frame>
        <population>The Per Protocol population was used for the secondary endpoint equivalence comparison which consisted of all randomized subjects that were dosed with 75%-125% of scheduled applications of Test or Reference and completed secondary endpoint evaluation on Study Day 8 +/- 2 days with no protocol violations that would affect treatment evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol Vaginal Cream</title>
            <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O2">
            <title>Estrace® 0.01% Cream</title>
            <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence</title>
          <description>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.</description>
          <population>The Per Protocol population was used for the secondary endpoint equivalence comparison which consisted of all randomized subjects that were dosed with 75%-125% of scheduled applications of Test or Reference and completed secondary endpoint evaluation on Study Day 8 +/- 2 days with no protocol violations that would affect treatment evaluation</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72"/>
                    <measurement group_id="O2" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence was established for the secondary endpoint if the 90% confidence interval for the difference of responder rates (test - reference) from baseline to Day 8 for the secondary endpoint is contained within [-0.20, 0.20], using the per-protocol population.</non_inferiority_desc>
            <param_type>Difference</param_type>
            <param_value>0.0500</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0687</ci_lower_limit>
            <ci_upper_limit>0.1686</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>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</title>
        <description>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.</description>
        <time_frame>Day 8</time_frame>
        <population>The Intent-to-treat (ITT) population was used for the Superiority Analysis which consisted of all randomized subjects that used at least one dose of Estradiol Vaginal Cream, Estrace®, or Placebo and returned for at least one post-baseline visit</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol Vaginal Cream</title>
            <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O2">
            <title>Estrace® 0.01% Cream</title>
            <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O3">
            <title>Placebo Vaginal Cream</title>
            <description>Placebo Vaginal Cream, administered once daily for 7 days.&#xD;
Placebo Vaginal Cream: Placebo Vaginal Cream (1 x 2 g for 7 days)</description>
          </group>
        </group_list>
        <measure>
          <title>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</title>
          <description>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.</description>
          <population>The Intent-to-treat (ITT) population was used for the Superiority Analysis which consisted of all randomized subjects that used at least one dose of Estradiol Vaginal Cream, Estrace®, or Placebo and returned for at least one post-baseline visit</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82"/>
                    <measurement group_id="O2" value="77"/>
                    <measurement group_id="O3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Both the test and reference products should both be statistically superior to placebo (p&lt;0.05, two-sided) using the Chi squared test with Yate's correction for the secondary endpoint responder rate, using the ITT study population and last observation carried forward. The compound hypothesis to test was: H0: PT - PP ≤ 0 versus HA: PT - PP &gt; 0; Where PT = cure rate of test treatment, and PP = cure rate of placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Superiority test of test product vs placebo</non_inferiority_desc>
            <p_value>0.1092</p_value>
            <method>Chi-squared</method>
            <param_type>Difference</param_type>
            <param_value>0.1387</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0280</ci_lower_limit>
            <ci_upper_limit>0.3054</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Both the test and reference products should both be statistically superior to placebo (p&lt;0.05, two-sided) using the Chi squared test with Yate's correction for the secondary endpoint responder rate, using the ITT study population and last observation carried forward. The compound hypothesis to test was: H0: PT - PP ≤ 0 versus HA: PT - PP &gt; 0; Where PT = cure rate of test treatment, and PP = cure rate of placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Superiority test of reference product vs placebo</non_inferiority_desc>
            <p_value>0.1805</p_value>
            <method>Chi-squared</method>
            <param_type>Difference</param_type>
            <param_value>0.1196</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0491</ci_lower_limit>
            <ci_upper_limit>0.2883</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from signing of the ICF until 30 days post study exit on Study Day 8.</time_frame>
      <desc>Adverse events were collected via subject self-reporting in a diary and queries at clinic visits. Only subjects that were confirmed to have received at least 1 dose of study medication were included in the Safety Population (i.e., At risk) for adverse event reporting. The Safety Population consisted of 146 subjects for the Estradiol Vaginal Cream arm, 144 subjects for the Estrace® arm, and 72 subjects for the Placebo arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Estradiol Vaginal Cream</title>
          <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.&#xD;
Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="E2">
          <title>Estrace® 0.01% Cream</title>
          <description>Estrace® 0.01% vaginal cream, administered once daily for 7 days.&#xD;
Estrace® 0.01% cream: Estrace® 0.01% vaginal cream (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="E3">
          <title>Placebo Vaginal Cream</title>
          <description>Placebo Vaginal Cream, administered once daily for 7 days.&#xD;
Placebo Vaginal Cream: Placebo Vaginal Cream (1 x 2 g for 7 days)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="146"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sick Sinus Syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Cardiac Arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Pericardial Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Cardiac Tamponade</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="146"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="144"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="146"/>
                <counts group_id="E2" events="22" subjects_affected="17" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="146"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="144"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vulvovaginal Pruritus</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="146"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="144"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Breast Tenderness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="146"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="144"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Vaginal Discharge</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="146"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="144"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Abhijit Barve, Head of Global Clinical Research</name_or_title>
      <organization>Mylan Inc.</organization>
      <email>abhijit.barve@mylan.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02195986
org study id: EVCR-11196
nct id: NCT02195986
lead sponsor: 
has dmc: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence
time frame: Study Day 8
description: 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.
measure: Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo
time frame: Study Day 8
description: 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.
measure: 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
description: 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.
measure: 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
description: 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.
arm group label: Estradiol Vaginal Cream
arm group type: Experimental
description: Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days.
arm group label: Estrace® 0.01% cream
arm group type: Active Comparator
description: Estrace® 0.01% vaginal cream, administered once daily for 7 days.
arm group label: Placebo Vaginal Cream
arm group type: Placebo Comparator
description: Placebo Vaginal Cream, administered once daily for 7 days.
intervention type: Drug
intervention name: Estradiol Vaginal Cream, 0.01%
description: Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)
arm group label: Estradiol Vaginal Cream
intervention type: Drug
intervention name: Estrace® 0.01% cream
description: Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)
arm group label: Estrace® 0.01% cream
intervention type: Drug
intervention name: Placebo Vaginal Cream
description: Placebo Vaginal Cream ( 1 x 2 g for 7 days)
arm group label: Placebo Vaginal Cream
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Matt Hummel, Ph.D.
role: Study Chair
affiliation: Mylan Pharmaceuticals Inc
last name: Ronald Ackerman, M.D.
role: Principal Investigator
affiliation: Comprehensive Clinical Trials, LLC
last name: James Andersen, M.D.
role: Principal Investigator
affiliation: Meridien Research
last name: Keith Aqua, M.D.
role: Principal Investigator
affiliation: Visions Clinical Research
last name: Theodore Cooper, M.D.
role: Principal Investigator
affiliation: Horizons Clinical Research Center, LLC
last name: Scott Eder, M.D.
role: Principal Investigator
affiliation: Women's Health Research Center/The Center for Women's Health & Wellness, LLC
last name: William Koltun, M.D.
role: Principal Investigator
affiliation: Medical Center for Clinical Research
last name: Gigi Lefebvre, M.D.
role: Principal Investigator
affiliation: Meridien Research
last name: Leonard Ranasinghe, M.D.
role: Principal Investigator
affiliation: Northern CA Research
last name: Rovena Reagan, M.D.
role: Principal Investigator
affiliation: Women's Health Care Research Corp.
last name: Ronald Surowitz, D.O.
role: Principal Investigator
affiliation: Health Awareness, Inc.
last name: Steven Sussman, M.D.
role: Principal Investigator
affiliation: Lawrence OB/GYN Clinical Research, LLC
last name: G. Michael Swor, M.D.
role: Principal Investigator
affiliation: Physician Care Clinical Research LLC
last name: Olga Tudela, M.D.
role: Principal Investigator
affiliation: Veritas Research., Corp.
last name: Arthur Waldbaum, M.D.
role: Principal Investigator
affiliation: Downtown Women's Health Care
last name: Maria C Fernandez, M.D.
role: Principal Investigator
affiliation: South Coast Research Center, Inc.
last name: Gary Carson, M.D
role: Principal Investigator
affiliation: Northern CA Research
last name: Lydie Hazan, M.D.
role: Principal Investigator
affiliation: Axis Clinical Trials
last name: Alfred Moffett, M.D.
role: Principal Investigator
affiliation: OB-GYN Associates of Mid Florida
last name: Tracey Lemon, M.D.
role: Principal Investigator
affiliation: Georgia Center for Women
last name: Steven Foley, M.D.
role: Principal Investigator
affiliation: MCB Clinical Research Centers, LLC
last name: Jason Haffizulla, M.D.
role: Principal Investigator
affiliation: Sunrise Medical Research, Inc.
last name: Robert Hunter, M.D.
role: Principal Investigator
affiliation: ARA-Arizona Research Associates
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country: United States
responsible party type: Sponsor
mesh term: Vaginitis
mesh term: Atrophic Vaginitis
mesh term: Atrophy
mesh term: Estradiol
sharing ipd: No
ipd description: N/A - Phase I study
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