<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/NCT03018106</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00088077</org_study_id>
    <nct_id>NCT03018106</nct_id>
  </id_info>
  <brief_title>Ospemifene vs. Conjugated Estrogens in the Treatment of Postmenopausal Sexual Dysfunction</brief_title>
  <official_title>Ospemifene Versus Conjugated Estrogens in the Treatment of Postmenopausal Sexual Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vulvovaginal atrophy (VVA) is a condition that impacts up to 60% of the growing&#xD;
      postmenopausal female population, and the most common symptom is dyspareunia. Vaginal&#xD;
      estrogen is the most common treatment for VVA, but it only marginally improves overall sexual&#xD;
      function, and many women and clinicians avoid using it because of the risks of exogenous&#xD;
      estrogen use during menopause. Ospemifene is a non-estrogen selective estrogen receptor&#xD;
      modulator (SERM) that is FDA-approved for treating dyspareunia related to VVA, and has shown&#xD;
      superb improvements in overall sexual health. 104 women will be randomized to receive 12&#xD;
      weeks of 60mg oral ospemifene, taken daily, or 12 weeks of 0.5mg vaginal conjugated&#xD;
      estrogens, which is placed vaginally twice per week. The improvements in sexual health and&#xD;
      VVA symptom severity will be compared in each group. This study will help determine if&#xD;
      ospemifene is a better treatment medication than conjugated estrogens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Female sexual dysfunction (FSD) affects 57% of postmenopausal women. Vulvovaginal atrophy&#xD;
      (VVA) is a condition that impacts up to 60% of the growing postmenopausal female population,&#xD;
      and the most common symptom is dyspareunia. Women with FSD are 3.84 times as likely to also&#xD;
      have VVA. Vaginal estrogen is the most common treatment for VVA, but it only marginally&#xD;
      improves overall sexual function, and many women and clinicians avoid using it because of the&#xD;
      risks of exogenous estrogen use during menopause. Ospemifene is a non-estrogen selective&#xD;
      estrogen receptor modulator (SERM) that is FDA-approved for treating dyspareunia related to&#xD;
      VVA, and has shown superb improvements in overall sexual health. This oral medication, taken&#xD;
      daily, improves vaginal health, and has demonstrated protective activity in the breast and&#xD;
      bone tissues. It also has not demonstrated any carcinogenic activity in the endometrium or&#xD;
      liver. This study hopes to determine if ospemifene is superior to conjugated estrogens in&#xD;
      improving sexual function and vaginal atrophy symptoms.&#xD;
&#xD;
      104 women will be randomized to receive 12 weeks of 60mg oral ospemifene, taken daily, or 12&#xD;
      weeks of 0.5mg vaginal conjugated estrogens, which is placed vaginally twice per week. Each&#xD;
      participant will be informed of her assigned medication, and will receive a medication coupon&#xD;
      to help offset the cost of the medication. Each medication is FDA-approved for long-term use&#xD;
      of at least 52 weeks. For this study, a 12-week prescription for the medication will be sent&#xD;
      electronically to the pharmacy of the participant's choice. The improvements in sexual health&#xD;
      and VVA symptom severity will be compared in each group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Obstacles with recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">June 30, 2017</start_date>
  <completion_date type="Actual">September 29, 2017</completion_date>
  <primary_completion_date type="Actual">September 29, 2017</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Female Sexual Function Index Score</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The Female Sexual Function Index (FSFI) is a 19 item questionnaire that asks about sexual function in the prior four weeks. The FSFI was developed for the specific purpose of assessing sexual arousal, orgasm, satisfaction, pain related to sexual functioning in clinical trial participants. Participants answer by selecting between 5-6 question-specific options to rate the degree to which the question fits their experience. Each response option is assigned a point and each question has 0-5 or 1-5 possible points. The points are summed to determine a total score. The total score can range from 2 to 36 and scores equal to or less than 26.55 indicate female sexual dysfunction (FSD).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain With Sex</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants reported pain with sex at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaginal Dryness</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants reported vaginal dryness at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaginal Itching</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants reported vaginal itching at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaginal Irritation</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants reported vaginal irritation at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Sexual Dysfunction, Physiological</condition>
  <arm_group>
    <arm_group_label>Ospemifene</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women randomized to this arm will receive 60mg oral ospemifene, taken daily, for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Estrogen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women randomized to this arm will receive 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ospemifene</intervention_name>
    <description>Ospemifene is a selective estrogen receptor modulator (SERM), and it is the only SERM approved in the United States to treat moderate to severe dyspareunia associated with VVA. It is an oral medication that is taken as a 60mg tablet once daily. Food intake increases its absorption by 2 to 3-fold, and this is not impacted by the fat or calorie content of the food. It is metabolized primarily in the liver, and is excreted in feces.</description>
    <arm_group_label>Ospemifene</arm_group_label>
    <other_name>Osphena</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaginal conjugated estrogens</intervention_name>
    <description>Conjugated estrogens are a mixture of several different estrogen salts derived from natural sources and blended to approximate the composition of estrogens in the urine of pregnant horses. The main components are sodium estrone sulphate and sodium equilin sulfate. Vaginal estrogen is considered the medication of choice for treating vulvovaginal atrophy (VVA).</description>
    <arm_group_label>Estrogen</arm_group_label>
    <other_name>Premarin Vaginal Cream</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Interested in resuming or continuing sexual activity&#xD;
&#xD;
          -  Greater than 12 months since last menstrual cycle or prior bilateral oophorectomy&#xD;
&#xD;
          -  Dyspareunia as a vulvovaginal atrophy symptom&#xD;
&#xD;
          -  Normal mammogram within 12 months prior to entry into the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or suspicion of breast carcinoma&#xD;
&#xD;
          -  History of hormone-dependent tumor&#xD;
&#xD;
          -  Genital bleeding of unknown cause&#xD;
&#xD;
          -  Ongoing vaginal infection&#xD;
&#xD;
          -  History of cerebrovascular accident (CVA), myocardial infarction (MI) or heart disease&#xD;
&#xD;
          -  Uncontrolled hypertension (HTN) over 160/100&#xD;
&#xD;
          -  Serious disease or chronic condition that may prevent completion of study&#xD;
&#xD;
          -  Body Mass Index (BMI) over 40&#xD;
&#xD;
          -  Hypercoagulable state, or currently on anticoagulant therapy&#xD;
&#xD;
          -  Use of any exogenous sex hormone within three months from study entry, or during the&#xD;
             study&#xD;
&#xD;
          -  Pelvic surgery within the last 12 months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gina Northington, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory Midtown Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory St. Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <results_first_submitted>December 1, 2017</results_first_submitted>
  <results_first_submitted_qc>December 1, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 20, 2017</results_first_posted>
  <last_update_submitted>December 28, 2017</last_update_submitted>
  <last_update_submitted_qc>December 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Gina Northington</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Female sexual disorder</keyword>
  <keyword>Aging</keyword>
  <keyword>Menopause</keyword>
  <keyword>Obstetrics/Gynecology</keyword>
  <keyword>Female urogenital disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sexual Dysfunction, Physiological</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estrogens</mesh_term>
    <mesh_term>Estrogens, Conjugated (USP)</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 27, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT03018106/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled between June 2017 and September 2017</recruitment_details>
      <pre_assignment_details>One individual gave informed consent to participate in the study and was randomized to the Estrogen arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ospemifene</title>
          <description>Women randomized to this arm were to receive 60mg oral ospemifene, taken daily, for 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>Estrogen</title>
          <description>Women randomized to this arm were to receive 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants consenting to take part in the trial are included in the baseline analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>Ospemifene</title>
          <description>Women randomized to this arm were to receive 60mg oral ospemifene, taken daily, for 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>Estrogen</title>
          <description>Women randomized to this arm were to receive 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
        </group>
        <group group_id="B3">
          <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="0"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
          </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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="B2" value="51" spread="0.0"/>
                    <measurement group_id="B3" value="51" spread="0.0"/>
                  </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="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Female Sexual Function Index Score</title>
        <description>The Female Sexual Function Index (FSFI) is a 19 item questionnaire that asks about sexual function in the prior four weeks. The FSFI was developed for the specific purpose of assessing sexual arousal, orgasm, satisfaction, pain related to sexual functioning in clinical trial participants. Participants answer by selecting between 5-6 question-specific options to rate the degree to which the question fits their experience. Each response option is assigned a point and each question has 0-5 or 1-5 possible points. The points are summed to determine a total score. The total score can range from 2 to 36 and scores equal to or less than 26.55 indicate female sexual dysfunction (FSD).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Estrogen</title>
            <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Female Sexual Function Index Score</title>
          <description>The Female Sexual Function Index (FSFI) is a 19 item questionnaire that asks about sexual function in the prior four weeks. The FSFI was developed for the specific purpose of assessing sexual arousal, orgasm, satisfaction, pain related to sexual functioning in clinical trial participants. Participants answer by selecting between 5-6 question-specific options to rate the degree to which the question fits their experience. Each response option is assigned a point and each question has 0-5 or 1-5 possible points. The points are summed to determine a total score. The total score can range from 2 to 36 and scores equal to or less than 26.55 indicate female sexual dysfunction (FSD).</description>
          <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pain With Sex</title>
        <description>Participants reported pain with sex at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Estrogen</title>
            <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Pain With Sex</title>
          <description>Participants reported pain with sex at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
          <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Vaginal Dryness</title>
        <description>Participants reported vaginal dryness at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Estrogen</title>
            <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Vaginal Dryness</title>
          <description>Participants reported vaginal dryness at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
          <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Vaginal Itching</title>
        <description>Participants reported vaginal itching at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Estrogen</title>
            <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Vaginal Itching</title>
          <description>Participants reported vaginal itching at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
          <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Vaginal Irritation</title>
        <description>Participants reported vaginal irritation at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Estrogen</title>
            <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Vaginal Irritation</title>
          <description>Participants reported vaginal irritation at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.</description>
          <population>The single participant was lost to follow up prior to completing the Week 12 assessment.</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from the time the participant consented to take part in the study through the Week 12 Visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Estrogen</title>
          <description>Women randomized to this arm received 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks</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="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT 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>
    <limitations_and_caveats>The patient population did not provide as many interested and qualified subjects as anticipated, thus the study was terminated early due to obstacles with recruitment and time limitations for data analyses.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Gina Northington, MD</name_or_title>
      <organization>Emory University</organization>
      <phone>(404) 778-5770</phone>
      <email>gina.northington@emory.edu</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/NCT03018106
org study id: IRB00088077
nct id: NCT03018106
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Vulvovaginal atrophy (VVA) is a condition that impacts up to 60% of the growing
      postmenopausal female population, and the most common symptom is dyspareunia. Vaginal
      estrogen is the most common treatment for VVA, but it only marginally improves overall sexual
      function, and many women and clinicians avoid using it because of the risks of exogenous
      estrogen use during menopause. Ospemifene is a non-estrogen selective estrogen receptor
      modulator (SERM) that is FDA-approved for treating dyspareunia related to VVA, and has shown
      superb improvements in overall sexual health. 104 women will be randomized to receive 12
      weeks of 60mg oral ospemifene, taken daily, or 12 weeks of 0.5mg vaginal conjugated
      estrogens, which is placed vaginally twice per week. The improvements in sexual health and
      VVA symptom severity will be compared in each group. This study will help determine if
      ospemifene is a better treatment medication than conjugated estrogens.
Female sexual dysfunction (FSD) affects 57% of postmenopausal women. Vulvovaginal atrophy
      (VVA) is a condition that impacts up to 60% of the growing postmenopausal female population,
      and the most common symptom is dyspareunia. Women with FSD are 3.84 times as likely to also
      have VVA. Vaginal estrogen is the most common treatment for VVA, but it only marginally
      improves overall sexual function, and many women and clinicians avoid using it because of the
      risks of exogenous estrogen use during menopause. Ospemifene is a non-estrogen selective
      estrogen receptor modulator (SERM) that is FDA-approved for treating dyspareunia related to
      VVA, and has shown superb improvements in overall sexual health. This oral medication, taken
      daily, improves vaginal health, and has demonstrated protective activity in the breast and
      bone tissues. It also has not demonstrated any carcinogenic activity in the endometrium or
      liver. This study hopes to determine if ospemifene is superior to conjugated estrogens in
      improving sexual function and vaginal atrophy symptoms.

      104 women will be randomized to receive 12 weeks of 60mg oral ospemifene, taken daily, or 12
      weeks of 0.5mg vaginal conjugated estrogens, which is placed vaginally twice per week. Each
      participant will be informed of her assigned medication, and will receive a medication coupon
      to help offset the cost of the medication. Each medication is FDA-approved for long-term use
      of at least 52 weeks. For this study, a 12-week prescription for the medication will be sent
      electronically to the pharmacy of the participant's choice. The improvements in sexual health
      and VVA symptom severity will be compared in each group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Female Sexual Function Index Score
time frame: Baseline, Week 12
description: The Female Sexual Function Index (FSFI) is a 19 item questionnaire that asks about sexual function in the prior four weeks. The FSFI was developed for the specific purpose of assessing sexual arousal, orgasm, satisfaction, pain related to sexual functioning in clinical trial participants. Participants answer by selecting between 5-6 question-specific options to rate the degree to which the question fits their experience. Each response option is assigned a point and each question has 0-5 or 1-5 possible points. The points are summed to determine a total score. The total score can range from 2 to 36 and scores equal to or less than 26.55 indicate female sexual dysfunction (FSD).
measure: Pain With Sex
time frame: Baseline, Week 12
description: Participants reported pain with sex at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
measure: Vaginal Dryness
time frame: Baseline, Week 12
description: Participants reported vaginal dryness at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
measure: Vaginal Itching
time frame: Baseline, Week 12
description: Participants reported vaginal itching at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
measure: Vaginal Irritation
time frame: Baseline, Week 12
description: Participants reported vaginal irritation at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
arm group label: Ospemifene
arm group type: Experimental
description: Women randomized to this arm will receive 60mg oral ospemifene, taken daily, for 12 weeks
arm group label: Estrogen
arm group type: Active Comparator
description: Women randomized to this arm will receive 0.5mg vaginal conjugated estrogens, placed vaginally twice per week, for 12 weeks
intervention type: Drug
intervention name: Ospemifene
description: Ospemifene is a selective estrogen receptor modulator (SERM), and it is the only SERM approved in the United States to treat moderate to severe dyspareunia associated with VVA. It is an oral medication that is taken as a 60mg tablet once daily. Food intake increases its absorption by 2 to 3-fold, and this is not impacted by the fat or calorie content of the food. It is metabolized primarily in the liver, and is excreted in feces.
arm group label: Ospemifene
other name: Osphena
intervention type: Drug
intervention name: Vaginal conjugated estrogens
description: Conjugated estrogens are a mixture of several different estrogen salts derived from natural sources and blended to approximate the composition of estrogens in the urine of pregnant horses. The main components are sodium estrone sulphate and sodium equilin sulfate. Vaginal estrogen is considered the medication of choice for treating vulvovaginal atrophy (VVA).
arm group label: Estrogen
other name: Premarin Vaginal Cream
criteria: 
gender: Female
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Gina Northington, MD, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Gina Northington
investigator title: Associate Professor
mesh term: Sexual Dysfunction, Physiological
mesh term: Estrogens
mesh term: Estrogens, Conjugated (USP)
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The patient population did not provide as many interested and qualified subjects as anticipated, thus the study was terminated early due to obstacles with recruitment and time limitations for data analyses.
point of contact: 