<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/NCT03249376</url>
  </required_header>
  <id_info>
    <org_study_id>ITI-007-404</org_study_id>
    <nct_id>NCT03249376</nct_id>
  </id_info>
  <brief_title>Lumateperone Monotherapy for the Treatment of Bipolar Depression Conducted Globally</brief_title>
  <official_title>A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Lumateperone Monotherapy in the Treatment of Patients With Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder (Bipolar Depression) Conducted Globally</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Intra-Cellular Therapies, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Intra-Cellular Therapies, Inc.</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>
      The study will evaluate the efficacy and safety of ITI-007 in a randomized, double-blind,&#xD;
      parallel-group, placebo-controlled, multi-center study in patients diagnosed with Bipolar I&#xD;
      or Bipolar II disorder having a major depressive episode.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 27, 2017</start_date>
  <completion_date type="Actual">March 1, 2019</completion_date>
  <primary_completion_date type="Actual">March 1, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <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>Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Baseline to Day 43</time_frame>
    <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score</measure>
    <time_frame>Baseline to Day 43</time_frame>
    <description>The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score</measure>
    <time_frame>Baseline to Day 43</time_frame>
    <description>The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">381</enrollment>
  <condition>Bipolar Depression</condition>
  <arm_group>
    <arm_group_label>Lumateperone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered once daily every evening for 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lumateperone</intervention_name>
    <description>Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
    <arm_group_label>Lumateperone</arm_group_label>
    <other_name>ITI-007</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Major Inclusion Criteria:&#xD;
&#xD;
          -  male or female subjects of any race, ages 18-75 inclusive, with a clinical diagnosis&#xD;
             of Bipolar I or Bipolar II disorder&#xD;
&#xD;
          -  experiencing a current major depressive episode&#xD;
&#xD;
          -  able to provide written informed consent&#xD;
&#xD;
        Major Exclusion Criteria:&#xD;
&#xD;
          -  any female subject who is pregnant or breast-feeding&#xD;
&#xD;
          -  any subject judged to be medically inappropriate for study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Kozauer, MD</last_name>
    <role>Study Director</role>
    <affiliation>Intra-Cellular Therapies, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Sherman Oaks</city>
        <state>California</state>
        <zip>91403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Joliet</city>
        <state>Illinois</state>
        <zip>60435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77381</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Bothell</city>
        <state>Washington</state>
        <zip>98011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Burgas</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Kardzhali</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Lovech</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Plovdiv</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Ruse</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Targovishte</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Tsarev Brod</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Varna</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Veliko Tarnovo</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Barranquilla</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Bello</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Pereira</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Ekaterinburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Nizhny Novgorod</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Omsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Samara</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Saratov</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Tomsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Belgrade</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Kragujevac</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Novi Sad</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Ivano-Frankivs'k</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Kherson</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Lviv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Odesa</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Poltava</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Smila</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Uzhgorod</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Vinnytsia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Colombia</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>April 20, 2022</results_first_submitted>
  <results_first_submitted_qc>May 10, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 3, 2022</results_first_posted>
  <disposition_first_submitted>April 9, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>May 10, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 3, 2022</disposition_first_posted>
  <last_update_submitted>May 10, 2022</last_update_submitted>
  <last_update_submitted_qc>May 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT03249376/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT03249376/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lumateperone</title>
          <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone (ITI-007 60 mg tosylate)</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="188">191 patients were randomized but only 188 patients received study drug. The number completed and discontinued is based on the 188 patients that received study drug.</participants>
                <participants group_id="P2" count="189">190 patients were randomized but only 189 patients received study drug. The number completed and discontinued is based on the 189 patients that received study drug.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="167"/>
                <participants group_id="P2" count="166"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>LTFU</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lumateperone</title>
          <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</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="188"/>
            <count group_id="B2" value="189"/>
            <count group_id="B3" value="377"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="45.7" spread="14.09"/>
                    <measurement group_id="B2" value="44.1" spread="12.87"/>
                    <measurement group_id="B3" value="44.9" spread="13.50"/>
                  </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="99"/>
                    <measurement group_id="B2" value="120"/>
                    <measurement group_id="B3" value="219"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian/White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="173"/>
                    <measurement group_id="B2" value="171"/>
                    <measurement group_id="B3" value="344"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </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="51"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ukraine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bulgaria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serbia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Colombia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montgomery-Asberg Depression Rating Scale (MADRS)</title>
          <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.8" spread="4.92"/>
                    <measurement group_id="B2" value="30.2" spread="4.65"/>
                    <measurement group_id="B3" value="30.5" spread="4.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score</title>
        <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.</description>
        <time_frame>Baseline to Day 43</time_frame>
        <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Lumateperone</title>
            <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score</title>
          <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.</description>
          <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="188"/>
                <count group_id="O2" value="188"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.70" spread="0.693"/>
                    <measurement group_id="O2" value="-12.12" spread="0.677"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Effects Model for Repeated Measure</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-4.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.89</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.34</ci_lower_limit>
            <ci_upper_limit>-2.83</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score</title>
        <description>The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.</description>
        <time_frame>Baseline to Day 43</time_frame>
        <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Lumateperone</title>
            <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score</title>
          <description>The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.</description>
          <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="188"/>
                <count group_id="O2" value="188"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.48" spread="0.170"/>
                    <measurement group_id="O2" value="-2.54" spread="0.167"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Effects Model for Repeated Measure</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.22</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.37</ci_lower_limit>
            <ci_upper_limit>-0.51</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score</title>
        <description>The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.</description>
        <time_frame>Baseline to Day 43</time_frame>
        <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Lumateperone</title>
            <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score</title>
          <description>The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.</description>
          <population>Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.</population>
          <units>Percent Score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="188"/>
                <count group_id="O2" value="188"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.4" spread="1.49"/>
                    <measurement group_id="O2" value="14.9" spread="1.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>4.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.42</ci_lower_limit>
            <ci_upper_limit>7.69</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From signing ICF until end of study procedures (~10 weeks), including 6 weeks of double-blind treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lumateperone</title>
          <description>Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks&#xD;
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo administered once daily every evening for 6 weeks&#xD;
Placebo: Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mania</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="188"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nauseau</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="188"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>ITI Clinical Trials</name_or_title>
      <organization>Intra-Cellular Therapies, Inc.</organization>
      <phone>646-440-9333</phone>
      <email>ITCIClinicalTrials@itci-inc.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249376
org study id: ITI-007-404
nct id: NCT03249376
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study will evaluate the efficacy and safety of ITI-007 in a randomized, double-blind,
      parallel-group, placebo-controlled, multi-center study in patients diagnosed with Bipolar I
      or Bipolar II disorder having a major depressive episode.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
time frame: Baseline to Day 43
description: The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
measure: Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score
time frame: Baseline to Day 43
description: The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.
measure: Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score
time frame: Baseline to Day 43
description: The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.
arm group label: Lumateperone
arm group type: Experimental
description: Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo administered once daily every evening for 6 weeks
intervention type: Drug
intervention name: Lumateperone
description: Lumateperone 42 mg (ITI-007 60 mg tosylate)
arm group label: Lumateperone
other name: ITI-007
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Susan Kozauer, MD
role: Study Director
affiliation: Intra-Cellular Therapies, Inc.
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country: Bulgaria
country: Colombia
country: Russian Federation
country: Serbia
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Bipolar Disorder
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 