<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/NCT03034018</url>
  </required_header>
  <id_info>
    <org_study_id>2016P002667</org_study_id>
    <nct_id>NCT03034018</nct_id>
  </id_info>
  <brief_title>Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia</brief_title>
  <official_title>A Double-blind, Randomized, Placebo-controlled Study to Determine the Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia in Midlife Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to determine the effect of suvorexant on insomnia symptoms in peri-&#xD;
      and postmenopausal women who are experiencing sleep difficulties related to nighttime hot&#xD;
      flashes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 25, 2017</start_date>
  <completion_date type="Actual">April 3, 2020</completion_date>
  <primary_completion_date type="Actual">April 3, 2020</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Within-person Change in ISI Score</measure>
    <time_frame>baseline and 4 weeks</time_frame>
    <description>The Insomnia Severity Index (ISI) is a scale comprising seven questions scored 0-3. The total ISI score is the sum of all questions, with a total range from 0-21 with higher values indicating worse insomnia. Within-person change in ISI score from baseline to 4 weeks was calculated.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Insomnia</condition>
  <arm_group>
    <arm_group_label>suvorexant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>suvorexant 10-20 mg taken at bedtime for four weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo taken at bedtime for four weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>suvorexant</intervention_name>
    <description>10-20 mg taken at bedtime for four weeks</description>
    <arm_group_label>suvorexant</arm_group_label>
    <other_name>Belsomra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo taken at bedtime for four weeks</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Peri- or postmenopausal women&#xD;
&#xD;
          -  DSM-5 criteria for Insomnia disorder, with onset of symptoms attributed to hot flashes&#xD;
&#xD;
          -  Some awakenings co-occur with a hot flash&#xD;
&#xD;
          -  Score on the Insomnia Severity Index (ISI) measure ≥15&#xD;
&#xD;
          -  Hot flashes present, including at night&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of other primary sleep disorders&#xD;
&#xD;
          -  Shift workers&#xD;
&#xD;
          -  Current or expected use of hypnotic medications&#xD;
&#xD;
          -  Current major depressive episode&#xD;
&#xD;
          -  Lifetime history of bipolar disorder, psychosis, or other serious mental health&#xD;
             problem&#xD;
&#xD;
          -  Current alcohol/substance use disorder&#xD;
&#xD;
          -  Obesity&#xD;
&#xD;
          -  Renal or hepatic disease&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Recent malignancy&#xD;
&#xD;
          -  Recent surgery&#xD;
&#xD;
          -  Neurological disorder or cardiovascular disease raising safety concerns&#xD;
&#xD;
          -  Medical instability considered to interfere with study procedures&#xD;
&#xD;
          -  Concomitant medications with drug interaction or co-administration concerns&#xD;
&#xD;
          -  Contraindications or allergic responses to suvorexant&#xD;
&#xD;
          -  Recent or planned travel across time zones&#xD;
&#xD;
          -  Excessive coffee or cigarette use&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hadine Joffe, MD MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <results_first_submitted>October 1, 2021</results_first_submitted>
  <results_first_submitted_qc>October 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2021</results_first_posted>
  <last_update_submitted>March 1, 2022</last_update_submitted>
  <last_update_submitted_qc>March 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Hadine Joffe, MD MSc</investigator_full_name>
    <investigator_title>Executive Director, Connors Center for Women's Health and Gender Biology</investigator_title>
  </responsible_party>
  <keyword>insomnia</keyword>
  <keyword>hot flashes</keyword>
  <keyword>menopause</keyword>
  <keyword>suvorexant</keyword>
  <keyword>belsomra</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <mesh_term>Hot Flashes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Suvorexant</mesh_term>
  </intervention_browse>
  <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>September 9, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03034018/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Suvorexant</title>
          <description>suvorexant 10-20 mg taken at bedtime for four weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>placebo taken at bedtime for four 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="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Initiated Assigned Treatment</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Suvorexant</title>
          <description>suvorexant 10-20 mg taken at bedtime for four weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>placebo taken at bedtime for four 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="27"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="56"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.2" spread="4.5"/>
                    <measurement group_id="B2" value="53.4" spread="3.9"/>
                    <measurement group_id="B3" value="54.3" spread="4.3"/>
                  </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="27"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="56"/>
                  </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>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </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="27"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Within-person Change in ISI Score</title>
        <description>The Insomnia Severity Index (ISI) is a scale comprising seven questions scored 0-3. The total ISI score is the sum of all questions, with a total range from 0-21 with higher values indicating worse insomnia. Within-person change in ISI score from baseline to 4 weeks was calculated.</description>
        <time_frame>baseline and 4 weeks</time_frame>
        <population>Participants who initiated treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Suvorexant</title>
            <description>suvorexant 10-20 mg taken at bedtime for four weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo taken at bedtime for four weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Within-person Change in ISI Score</title>
          <description>The Insomnia Severity Index (ISI) is a scale comprising seven questions scored 0-3. The total ISI score is the sum of all questions, with a total range from 0-21 with higher values indicating worse insomnia. Within-person change in ISI score from baseline to 4 weeks was calculated.</description>
          <population>Participants who initiated treatment</population>
          <units>score 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="27"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.1" lower_limit="-10.2" upper_limit="-6.0"/>
                    <measurement group_id="O2" value="-5.6" lower_limit="-7.4" upper_limit="-3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Suvorexant</title>
          <description>suvorexant 10-20 mg taken at bedtime for four weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>placebo taken at bedtime for four 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="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_assessment>Non-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="10" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>gastro-intestinal symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>somnolence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>dry mouth</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>mood symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </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>
    <point_of_contact>
      <name_or_title>Hadine Joffe, MD MSc</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-732-4906</phone>
      <email>hjoffe@bwh.harvard.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/NCT03034018
org study id: 2016P002667
nct id: NCT03034018
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The aim of this study is to determine the effect of suvorexant on insomnia symptoms in peri-
      and postmenopausal women who are experiencing sleep difficulties related to nighttime hot
      flashes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Within-person Change in ISI Score
time frame: baseline and 4 weeks
description: The Insomnia Severity Index (ISI) is a scale comprising seven questions scored 0-3. The total ISI score is the sum of all questions, with a total range from 0-21 with higher values indicating worse insomnia. Within-person change in ISI score from baseline to 4 weeks was calculated.
arm group label: suvorexant
arm group type: Experimental
description: suvorexant 10-20 mg taken at bedtime for four weeks
arm group label: placebo
arm group type: Placebo Comparator
description: placebo taken at bedtime for four weeks
intervention type: Drug
intervention name: suvorexant
description: 10-20 mg taken at bedtime for four weeks
arm group label: suvorexant
other name: Belsomra
intervention type: Drug
intervention name: placebo
description: placebo taken at bedtime for four weeks
arm group label: placebo
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hadine Joffe, MD MSc
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Hadine Joffe, MD MSc
investigator title: Executive Director, Connors Center for Women's Health and Gender Biology
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Hot Flashes
mesh term: Suvorexant
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 