<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/NCT02995694</url>
  </required_header>
  <id_info>
    <org_study_id>71462901</org_study_id>
    <nct_id>NCT02995694</nct_id>
  </id_info>
  <brief_title>A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis</brief_title>
  <official_title>Clinical Endpoint Therapeutic Equivalence Multi-Site Study Comparing Estradiol Vaginal Cream (0.01%; Alvogen Pine Brook LLC.) to Estrace® Cream (0.01%; Warner Chilcott) in Postmenopausal Females With Atrophic Vaginitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alvogen Pine Brook LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alvogen Pine Brook LLC</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 Alvogen'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>
  <detailed_description>
    <textblock>
      This randomized, double-blind, placebo-controlled, parallel group, multiple-site study was&#xD;
      designed to evaluate the therapeutic efficacy and safety of a generic Estradiol Vaginal Cream&#xD;
      USP, 0.01% (Alvogen Pine Brook LLC) compared to the FDA Reference Listed Drug (RLD), Estrace®&#xD;
      (estradiol vaginal cream USP, 0.01%, Warner Chilcott) in patients with atrophic vaginitis.&#xD;
      Additionally, both the Test and the RLD formulations were tested for superiority against a&#xD;
      Placebo.&#xD;
&#xD;
      Following the 14-day screening period, patients who continued to meet the inclusion/exclusion&#xD;
      criteria were randomized in a 2:2:1 ratio (Test: Reference: Placebo) for 7 days of treatment.&#xD;
&#xD;
      Five hundred and thirty-five (535) patients were randomized to one of the three study&#xD;
      products as follows:&#xD;
&#xD;
        -  Test: Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC)&#xD;
&#xD;
        -  Reference: Estrace® (estradiol vaginal cream USP, 0.01%) (Warner Chilcott)&#xD;
&#xD;
        -  Placebo: Test product vehicle cream (Alvogen Pine Brook LLC)&#xD;
&#xD;
      Patients completed up to three clinic visits as follows:&#xD;
&#xD;
        -  Visit 1 - Screening: Day -14 to Day -1&#xD;
&#xD;
        -  Visit 2 - Randomization: Day 1&#xD;
&#xD;
        -  Visit 3 - End of Study: Day 8, maximum Day 10&#xD;
&#xD;
      Study product was self-administered by the patient for 7 days according to the dosing&#xD;
      instructions provided. Each patient was required to dose once daily at approximately the me&#xD;
      of day for 7 consecutive days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2016</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vaginal Cytology</measure>
    <time_frame>Day 8</time_frame>
    <description>Number of patients in PP population identified as responders at end of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy</measure>
    <time_frame>Day 8</time_frame>
    <description>Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A &quot;Treatment Success&quot; was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">535</enrollment>
  <condition>Atrophic Vaginitis</condition>
  <arm_group>
    <arm_group_label>Test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol Vaginal Cream</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference.</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Estrace Vaginal Cream</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo with no active pharmaceutical ingredients. Topical vaginal cream</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol</intervention_name>
    <description>Estradiol Vaginal Cream</description>
    <arm_group_label>Test</arm_group_label>
    <other_name>Estadiol Vaginal Cream</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo with no active pharmaceutical ingredients. Topical vaginal cream</description>
    <arm_group_label>Placebos</arm_group_label>
    <other_name>Topical Vaginal Cream</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reference</intervention_name>
    <description>Estrace Vaginal Cream</description>
    <arm_group_label>Reference.</arm_group_label>
    <other_name>Topical Vaginal Cream</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent that meets all criteria of current FDA regulations&#xD;
&#xD;
          2. Females age: 30-75 years old inclusive who are postmenopausal.&#xD;
&#xD;
          3. 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. Hysterectomy without&#xD;
             oophorectomy if of age that investigator believes would have naturally reached 12&#xD;
             months of spontaneous amenorrhea.&#xD;
&#xD;
          4. 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;
                  *provided that patient is currently sexually active and plans to remain so&#xD;
                  throughout study.&#xD;
&#xD;
          5. Normal breast exam at screening and mammogram completed within 9 months prior to&#xD;
             screening in patients &gt;40 years old.&#xD;
&#xD;
          6. For women with an intact uterus, an endometrial thickness &lt; 4 mm as determined by&#xD;
             vaginal ultrasonography.&#xD;
&#xD;
          7. Documented PAP smear conducted within previous 12 months with no findings that the&#xD;
             Investigator believes would contraindicate the use of topical vaginal estradiol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Females younger than 30 years of age or older than 75 years of age&#xD;
&#xD;
          2. Patients with a serum FSH level of ≤ 40mIU/ml at screening.&#xD;
&#xD;
          3. Greater than 5% superficial cells on vaginal cytology.&#xD;
&#xD;
          4. Vaginal pH ≤ 5&#xD;
&#xD;
          5. Significant history or current evidence of chronic infectious disease, system&#xD;
             disorder, organ disorder (including significant liver/kidney impairment) or other&#xD;
             medical condition that in the Investigator's opinion would place the study patient at&#xD;
             undue risk by participation or could jeopardize the integrity of the study&#xD;
             evaluations.&#xD;
&#xD;
          6. Patients with an intact uterus should have vaginal ultrasonography results to confirm&#xD;
             an inactive endometrial lining. Patients with an endometrial thickness equal to or&#xD;
             greater than 4mm should be excluded.&#xD;
&#xD;
          7. Patients with known, suspected or current history of carcinoma of the breast. All&#xD;
             patients over the age of 40 must have had a mammogram performed within 9 months of the&#xD;
             study start and all patients will have a physical breast exam performed at screening.&#xD;
&#xD;
          8. Patients with baseline systolic blood pressure of &gt; 150mm Hg and/or diastolic pressure&#xD;
             &gt; 90 mm Hg&#xD;
&#xD;
          9. Any patient with undiagnosed vaginal bleeding or significant risk factors for&#xD;
             endometrial cancer.&#xD;
&#xD;
         10. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meena Venugopal, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Alvogen Pine Brook LLC</affiliation>
  </overall_official>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <results_first_submitted>May 15, 2019</results_first_submitted>
  <results_first_submitted_qc>November 30, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 1, 2021</results_first_posted>
  <last_update_submitted>November 30, 2021</last_update_submitted>
  <last_update_submitted_qc>November 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Test</title>
          <description>Estradiol Vaginal Cream&#xD;
Estradiol: Estradiol Vaginal Cream</description>
        </group>
        <group group_id="P2">
          <title>Reference.</title>
          <description>Estrace Vaginal Cream&#xD;
Reference: Estrace Vaginal Cream</description>
        </group>
        <group group_id="P3">
          <title>Placebos</title>
          <description>Placebo with no active pharmaceutical ingredients. Topical vaginal cream&#xD;
Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="215"/>
                <participants group_id="P2" count="211"/>
                <participants group_id="P3" count="109"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="181"/>
                <participants group_id="P2" count="183"/>
                <participants group_id="P3" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Estradiol Vaginal Cream</title>
          <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days. 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 Vaginal Cream</title>
          <description>Estrace Vaginal Cream, 0.01%, administered once daily for 7 days. Estrace Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo Cream, administered once daily for 7 days. Placebo 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="181"/>
            <count group_id="B2" value="183"/>
            <count group_id="B3" value="94"/>
            <count group_id="B4" value="458"/>
          </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="167"/>
                    <measurement group_id="B2" value="172"/>
                    <measurement group_id="B3" value="89"/>
                    <measurement group_id="B4" value="428"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.0" lower_limit="42" upper_limit="75"/>
                    <measurement group_id="B2" value="59.4" lower_limit="45" upper_limit="74"/>
                    <measurement group_id="B3" value="59.9" lower_limit="47" upper_limit="74"/>
                    <measurement group_id="B4" value="59.4" lower_limit="42" upper_limit="75"/>
                  </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="181"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="94"/>
                    <measurement group_id="B4" value="458"/>
                  </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="62"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="159"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="119"/>
                    <measurement group_id="B2" value="116"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="299"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <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="14"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="165"/>
                    <measurement group_id="B2" value="155"/>
                    <measurement group_id="B3" value="85"/>
                    <measurement group_id="B4" value="405"/>
                  </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="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="181"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="94"/>
                    <measurement group_id="B4" value="458"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Vaginal Cytology</title>
        <description>Number of patients in PP population identified as responders at end of the study.</description>
        <time_frame>Day 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Test</title>
            <description>Estradiol Vaginal Cream&#xD;
Estradiol: Estradiol Vaginal Cream</description>
          </group>
          <group group_id="O2">
            <title>Reference.</title>
            <description>Estrace Vaginal Cream&#xD;
Reference: Estrace Vaginal Cream</description>
          </group>
          <group group_id="O3">
            <title>Placebos</title>
            <description>Placebo with no active pharmaceutical ingredients. Topical vaginal cream&#xD;
Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream</description>
          </group>
        </group_list>
        <measure>
          <title>Vaginal Cytology</title>
          <description>Number of patients in PP population identified as responders at end of the study.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy</title>
        <description>Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A &quot;Treatment Success&quot; was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.</description>
        <time_frame>Day 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Estradiol Vaginal Cream</title>
            <description>Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days. Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days)</description>
          </group>
          <group group_id="O2">
            <title>Reference</title>
            <description>Estrace Vaginal Cream</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo arm</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy</title>
          <description>Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A &quot;Treatment Success&quot; was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="115"/>
                    <measurement group_id="O2" value="114"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 months</time_frame>
      <desc>There was one SAE, a death, reported for a subject during screening who had not yet been randomized into the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Test</title>
          <description>Estradiol Vaginal Cream&#xD;
Estradiol: Estradiol Vaginal Cream</description>
        </group>
        <group group_id="E2">
          <title>Reference.</title>
          <description>Estrace Vaginal Cream&#xD;
Reference: Estrace Vaginal Cream</description>
        </group>
        <group group_id="E3">
          <title>Placebos</title>
          <description>Placebo with no active pharmaceutical ingredients. Topical vaginal cream&#xD;
Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream</description>
        </group>
      </group_list>
      <serious_events>
        <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="215"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="109"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="88" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="85" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous System Disorders</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric disorders</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="109"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast Tenderness</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="215"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="211"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="109"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Meena Venugopal</name_or_title>
      <organization>Alvogen Pine Brook</organization>
      <phone>973-532-7824</phone>
      <email>meena.venugopal@alvogen.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/NCT02995694
org study id: 71462901
nct id: NCT02995694
lead sponsor: 
has dmc: No
The purpose of this study is to determine the therapeutic equivalence of Alvogen'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.
This randomized, double-blind, placebo-controlled, parallel group, multiple-site study was
      designed to evaluate the therapeutic efficacy and safety of a generic Estradiol Vaginal Cream
      USP, 0.01% (Alvogen Pine Brook LLC) compared to the FDA Reference Listed Drug (RLD), Estrace®
      (estradiol vaginal cream USP, 0.01%, Warner Chilcott) in patients with atrophic vaginitis.
      Additionally, both the Test and the RLD formulations were tested for superiority against a
      Placebo.

      Following the 14-day screening period, patients who continued to meet the inclusion/exclusion
      criteria were randomized in a 2:2:1 ratio (Test: Reference: Placebo) for 7 days of treatment.

      Five hundred and thirty-five (535) patients were randomized to one of the three study
      products as follows:

        -  Test: Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC)

        -  Reference: Estrace® (estradiol vaginal cream USP, 0.01%) (Warner Chilcott)

        -  Placebo: Test product vehicle cream (Alvogen Pine Brook LLC)

      Patients completed up to three clinic visits as follows:

        -  Visit 1 - Screening: Day -14 to Day -1

        -  Visit 2 - Randomization: Day 1

        -  Visit 3 - End of Study: Day 8, maximum Day 10

      Study product was self-administered by the patient for 7 days according to the dosing
      instructions provided. Each patient was required to dose once daily at approximately the me
      of day for 7 consecutive days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Vaginal Cytology
time frame: Day 8
description: Number of patients in PP population identified as responders at end of the study.
measure: Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy
time frame: Day 8
description: Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A "Treatment Success" was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
arm group label: Test
arm group type: Experimental
description: Estradiol Vaginal Cream
arm group label: Reference.
arm group type: Active Comparator
description: Estrace Vaginal Cream
arm group label: Placebos
arm group type: Placebo Comparator
description: Placebo with no active pharmaceutical ingredients. Topical vaginal cream
intervention type: Drug
intervention name: Estradiol
description: Estradiol Vaginal Cream
arm group label: Test
other name: Estadiol Vaginal Cream
intervention type: Drug
intervention name: Placebos
description: Placebo with no active pharmaceutical ingredients. Topical vaginal cream
arm group label: Placebos
other name: Topical Vaginal Cream
intervention type: Drug
intervention name: Reference
description: Estrace Vaginal Cream
arm group label: Reference.
other name: Topical Vaginal Cream
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Meena Venugopal, Ph.D.
role: Study Chair
affiliation: Alvogen Pine Brook LLC
responsible party type: Sponsor
mesh term: Vaginitis
mesh term: Atrophic Vaginitis
mesh term: Atrophy
mesh term: Estradiol
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 