<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/NCT01680900</url>
  </required_header>
  <id_info>
    <org_study_id>816164</org_study_id>
    <nct_id>NCT01680900</nct_id>
  </id_info>
  <brief_title>Vilazodone for Menopausal Hot Flashes</brief_title>
  <official_title>Vilazodone for Menopausal Hot Flashes: A Proof in Principle Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Forest Laboratories</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to determine proof in principle that vilazodone, a selective serotonin&#xD;
      reuptake inhibitor and 5HT1a agonist, reduces the frequency and severity of menopausal hot&#xD;
      flashes relative to placebo. A secondary aim is to evaluate improvement in menopause-related&#xD;
      quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a proposal to conduct a small clinical trial for proof in principle that vilazodone&#xD;
      reduces the frequency and severity of menopausal hot flashes. An additional exploratory aim&#xD;
      is to identify improvement in menopause-related quality of life. Healthy, perimenopausal&#xD;
      women ages 45-60 with an average of 4 or more moderate or severe hot flashes/night sweats per&#xD;
      day for 3 screening weeks will be randomized to 8 weeks of treatment in a 2:1 ratio of&#xD;
      vilazodone or matching placebo pills. Flexible dosing of vilazodone will start at 10 mg&#xD;
      once/day for 7 days, increase to 20 mg/day for 1 more week and increase to 40 mg once/day at&#xD;
      week 3 if unimproved. The primary outcome assessments are the frequency and severity of hot&#xD;
      flashes at week 4 and week 8 as assessed by prospective daily diaries (using 7-day mean&#xD;
      scores from the daily diaries). The secondary outcome is clinical improvement, defined as hot&#xD;
      flash frequency &gt;=50% decrease from baseline. Treatment-emergent adverse events will be&#xD;
      monitored and patient ratings of tolerability will be obtained.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>N/A</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>Daily Diary Ratings of Frequency of Hot Flashes</measure>
    <time_frame>Week 8.</time_frame>
    <description>Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Daily Diary Ratings of Severity of Hot Flashes</measure>
    <time_frame>Week 8.</time_frame>
    <description>Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Patients With &gt;=50% Reduction in Moderate to Severe Hot Flashes</measure>
    <time_frame>Percent change from baseline at Week 8</time_frame>
    <description>Percent of patients with n &gt;=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Menopause-related Quality of Life (MENQOL)</measure>
    <time_frame>Week 8</time_frame>
    <description>The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percentage of Participants That Were Satisfied or Very Satisfied</measure>
    <time_frame>Week 8</time_frame>
    <description>Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).</description>
  </other_outcome>
  <other_outcome>
    <measure>Sheehan Global Ratings of Symptom (Hot Flash)Interference</measure>
    <time_frame>Change from Baseline at Week 8</time_frame>
    <description>Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Hot Flushes</condition>
  <arm_group>
    <arm_group_label>experimental 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo capsules (sugar pill)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsules matched to the drug dose for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vilazodone</intervention_name>
    <description>capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
    <arm_group_label>experimental 1</arm_group_label>
    <other_name>viibryd</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo capsules</intervention_name>
    <description>placebo capsules matched to drug capsules.</description>
    <arm_group_label>placebo capsules (sugar pill)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women ages 45-60 years&#xD;
&#xD;
          -  Amenorrhea for 60 days or more or postmenopausal or bi-lateral oophorectomy.&#xD;
&#xD;
          -  4 or more moderate or severe hot flashes or night sweats per 24 hour period (28/week)&#xD;
             as recorded on daily diaries in 3 screening weeks.&#xD;
&#xD;
          -  Hot flashes/night sweats rated as moderate to severe and/or bothersome (moderately to&#xD;
             a lot) on 4 or more days/nights in each screen week.&#xD;
&#xD;
          -  In general good health.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychotropic medications currently or within the last 30 days.&#xD;
&#xD;
          -  Current use of hormonal medications such as hormone therapy or hormonal contraception&#xD;
             or any treatment for hot flashes (Prescription, over-the-counter or herbal).&#xD;
&#xD;
          -  Drug or alcohol abuse in the past year.&#xD;
&#xD;
          -  Lifetime diagnosis of psychosis or bipolar disorder.&#xD;
&#xD;
          -  Suicide attempt in the past 3 years or any current suicidal ideation.&#xD;
&#xD;
          -  Current major depression.&#xD;
&#xD;
          -  Not using a medically approved, non-hormonal method of birth control if sexually&#xD;
             active and not postmenopausal (12 or more months since last menstrual period or&#xD;
             bi-lateral oophorectomy).&#xD;
&#xD;
          -  Pregnancy, intending pregnancy or breast feeding.&#xD;
&#xD;
          -  Any severe of unstable medical illness, e.g., breast or ovarian cancer, seizure&#xD;
             disorders, etc.&#xD;
&#xD;
          -  Current participation in another intervention study.&#xD;
&#xD;
          -  Inability or unwillingness to complete study procedures.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ellen W Freeman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dept OB/GYN, Mudd Professorship Suite</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <results_first_submitted>December 4, 2014</results_first_submitted>
  <results_first_submitted_qc>January 13, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 14, 2015</results_first_posted>
  <last_update_submitted>January 13, 2015</last_update_submitted>
  <last_update_submitted_qc>January 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 14, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Ellen Freeman</investigator_full_name>
    <investigator_title>Research Profesor</investigator_title>
  </responsible_party>
  <keyword>menopause</keyword>
  <keyword>hot flashes</keyword>
  <keyword>vilazodone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hot Flashes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vilazodone Hydrochloride</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental 1</title>
          <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Capsules (Sugar Pill)</title>
          <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Experimental 1</title>
          <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Capsules (Sugar Pill)</title>
          <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</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="24"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>self-reported age in years</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.5" spread="3.7"/>
                    <measurement group_id="B2" value="52.7" spread="4.2"/>
                    <measurement group_id="B3" value="51.9" spread="3.9"/>
                  </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="24"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="36"/>
                  </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_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="24"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Daily Diary Ratings of Frequency of Hot Flashes</title>
        <description>Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.</description>
        <time_frame>Week 8.</time_frame>
        <population>all participants randomized to treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Diary Ratings of Frequency of Hot Flashes</title>
          <description>Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.</description>
          <population>all participants randomized to treatment</population>
          <units>number of hot flashes</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.65" lower_limit="2.57" upper_limit="4.73"/>
                    <measurement group_id="O2" value="4.71" lower_limit="3.61" upper_limit="5.80"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.05</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.60</ci_lower_limit>
            <ci_upper_limit>-0.48</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Patients With &gt;=50% Reduction in Moderate to Severe Hot Flashes</title>
        <description>Percent of patients with n &gt;=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries</description>
        <time_frame>Percent change from baseline at Week 8</time_frame>
        <population>all participants with at least one treatment response</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Patients With &gt;=50% Reduction in Moderate to Severe Hot Flashes</title>
          <description>Percent of patients with n &gt;=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries</description>
          <population>all participants with at least one treatment response</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="83"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Menopause-related Quality of Life (MENQOL)</title>
        <description>The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.</description>
        <time_frame>Week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Menopause-related Quality of Life (MENQOL)</title>
          <description>The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.89" lower_limit="1.55" upper_limit="2.24"/>
                    <measurement group_id="O2" value="2.08" lower_limit="1.63" upper_limit="2.53"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.75</ci_lower_limit>
            <ci_upper_limit>-0.08</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Adverse Events</title>
        <description>A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Participants That Were Satisfied or Very Satisfied</title>
        <description>Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).</description>
        <time_frame>Week 8</time_frame>
        <population>all participants with at least one treatment response.</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants That Were Satisfied or Very Satisfied</title>
          <description>Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).</description>
          <population>all participants with at least one treatment response.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Sheehan Global Ratings of Symptom (Hot Flash)Interference</title>
        <description>Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.</description>
        <time_frame>Change from Baseline at Week 8</time_frame>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Daily Diary Ratings of Severity of Hot Flashes</title>
        <description>Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).</description>
        <time_frame>Week 8.</time_frame>
        <population>all participants randomized to treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental 1</title>
            <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Capsules (Sugar Pill)</title>
            <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Diary Ratings of Severity of Hot Flashes</title>
          <description>Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).</description>
          <population>all participants randomized to treatment</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17" lower_limit="1.05" upper_limit="1.80"/>
                    <measurement group_id="O2" value="1.39" lower_limit="1.02" upper_limit="1.76"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.05</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.74</ci_lower_limit>
            <ci_upper_limit>-0.21</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Experimental 1</title>
          <description>vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks&#xD;
vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Capsules (Sugar Pill)</title>
          <description>Placebo capsules matched to the drug dose for 8 weeks&#xD;
placebo capsules: placebo capsules matched to drug capsules.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </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="17" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
              </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 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>
    <point_of_contact>
      <name_or_title>Dr. Ellen Freeman</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>215-662-3329</phone>
      <email>freemane@mail.med.upenn.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/NCT01680900
org study id: 816164
nct id: NCT01680900
lead sponsor: 
collaborator: 
has dmc: No
This is a pilot study to determine proof in principle that vilazodone, a selective serotonin
      reuptake inhibitor and 5HT1a agonist, reduces the frequency and severity of menopausal hot
      flashes relative to placebo. A secondary aim is to evaluate improvement in menopause-related
      quality of life.
This is a proposal to conduct a small clinical trial for proof in principle that vilazodone
      reduces the frequency and severity of menopausal hot flashes. An additional exploratory aim
      is to identify improvement in menopause-related quality of life. Healthy, perimenopausal
      women ages 45-60 with an average of 4 or more moderate or severe hot flashes/night sweats per
      day for 3 screening weeks will be randomized to 8 weeks of treatment in a 2:1 ratio of
      vilazodone or matching placebo pills. Flexible dosing of vilazodone will start at 10 mg
      once/day for 7 days, increase to 20 mg/day for 1 more week and increase to 40 mg once/day at
      week 3 if unimproved. The primary outcome assessments are the frequency and severity of hot
      flashes at week 4 and week 8 as assessed by prospective daily diaries (using 7-day mean
      scores from the daily diaries). The secondary outcome is clinical improvement, defined as hot
      flash frequency >=50% decrease from baseline. Treatment-emergent adverse events will be
      monitored and patient ratings of tolerability will be obtained.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Daily Diary Ratings of Frequency of Hot Flashes
time frame: Week 8.
description: Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.
measure: Daily Diary Ratings of Severity of Hot Flashes
time frame: Week 8.
description: Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).
measure: Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes
time frame: Percent change from baseline at Week 8
description: Percent of patients with n >=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries
measure: Menopause-related Quality of Life (MENQOL)
time frame: Week 8
description: The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.
measure: Number of Participants With Adverse Events
time frame: Baseline and Week 12
description: A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.
measure: Percentage of Participants That Were Satisfied or Very Satisfied
time frame: Week 8
description: Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).
measure: Sheehan Global Ratings of Symptom (Hot Flash)Interference
time frame: Change from Baseline at Week 8
description: Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.
arm group label: experimental 1
arm group type: Experimental
description: vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks
arm group label: placebo capsules (sugar pill)
arm group type: Placebo Comparator
description: Placebo capsules matched to the drug dose for 8 weeks
intervention type: Drug
intervention name: vilazodone
description: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.
arm group label: experimental 1
other name: viibryd
intervention type: Drug
intervention name: placebo capsules
description: placebo capsules matched to drug capsules.
arm group label: placebo capsules (sugar pill)
criteria: 
gender: Female
minimum age: 45 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ellen W Freeman, PhD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Ellen Freeman
investigator title: Research Profesor
mesh term: Hot Flashes
mesh term: Vilazodone Hydrochloride
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 