<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/NCT01725282</url>
  </required_header>
  <id_info>
    <org_study_id>6949-CL-0005</org_study_id>
    <nct_id>NCT01725282</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect and Safety of Quetiapine Extended Release (XR) (FK949E) in Major Depressive Disorder</brief_title>
  <official_title>Phase 2 Study of FK949E - Double-blind, Placebo-controlled, Comparative Study in Major Depressive Disorder Patients With Inadequate Response to Existing Antidepressants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, quetiapine XR or placebo will be administered orally for 6 weeks to major&#xD;
      depressive disorder patients with lack of response to existing antidepressants, with the aim&#xD;
      of evaluating the efficacy of quetiapine XR and dose-response in three quetiapine XR dose&#xD;
      groups based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2011</start_date>
  <completion_date type="Actual">August 24, 2013</completion_date>
  <primary_completion_date type="Actual">August 24, 2013</primary_completion_date>
  <phase>Phase 2</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>Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The 17-item Hamilton Depression Scale (HAM-D17) is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 52 where a higher score indicates a greater depressive state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened.&#xD;
Improvement is defined as a score of 1 or 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are:&#xD;
Limitation in physical activities because of health problems.&#xD;
Limitations in usual role activities because of physical health problems.&#xD;
Bodily pain.&#xD;
Limitations in social activities because of physical or emotional problems.&#xD;
General mental health (psychological distress and well-being).&#xD;
Limitations in usual role activities because of emotional problems.&#xD;
Vitality (energy and fatigue).&#xD;
General health perception.&#xD;
Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven &quot;component&quot; scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">172</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quetiapine 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quetiapine 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quetiapine 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>quetiapine extended release (XR)</intervention_name>
    <description>Extended release tablets</description>
    <arm_group_label>Quetiapine 150 mg</arm_group_label>
    <arm_group_label>Quetiapine 300 mg</arm_group_label>
    <arm_group_label>Quetiapine 50 mg</arm_group_label>
    <other_name>Seroquel XR</other_name>
    <other_name>FK949E</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>matching tablets</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of major depressive disorder as specified in the Diagnostic and Statistical&#xD;
             Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) with the use of the&#xD;
             Mini-International Neuropsychiatric Interview (M.I.N.I.)&#xD;
&#xD;
          -  Documented appropriate treatment history (i.e., lack of response to treatment at&#xD;
             labeled dosage for at least 4 weeks) for the current major depression episode with an&#xD;
             antidepressant other than that used concomitantly with the study drug&#xD;
&#xD;
          -  The Hamilton Depression Rating Scale (HAM-D17) total score of 20 points or more and&#xD;
             HAM-D17 depressed mood score of 2 points or more&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent or previous history of DSM-IV-TR Axis I disorders, except major depressive&#xD;
             disorder, within the last 6 months before informed consent&#xD;
&#xD;
          -  Concurrence of DSM-IV-TR Axis II disorder that is considered to greatly affect&#xD;
             patient's current mental status&#xD;
&#xD;
          -  The duration of the current major depression episode is shorter than 4 weeks or longer&#xD;
             than 24 months at informed consent&#xD;
&#xD;
          -  History of dependence of substances other than caffeine and nicotine or history of&#xD;
             abuse or dependence of alcohol&#xD;
&#xD;
          -  The HAM-D17 suicide score of 3 points or more, history of suicide attempt within the&#xD;
             last 6 months before informed consent, or the risk of suicide in the investigator's or&#xD;
             subinvestigator's opinion&#xD;
&#xD;
          -  Concurrent or previous history of diabetes mellitus. HbA1c levels of 6.1% (Japan&#xD;
             Diabetes Society values) or more within the past 2 months&#xD;
&#xD;
          -  Electroconvulsive therapy within the last 62 days before primary registration (within&#xD;
             the last 90 days before secondary registration)&#xD;
&#xD;
          -  Treatment with a depot antipsychotic within the last 28 days&#xD;
&#xD;
          -  Documented or suspected (to be a carrier of) conditions such as renal failure, hepatic&#xD;
             failure, serious cardiac disease (or current use of antiarrhythmic drugs), hepatitis&#xD;
             B, hepatitis C, or acquired immunodeficiency syndrome (AIDS)&#xD;
&#xD;
          -  Concurrence of uncontrolled hypertension (defined as a systolic blood pressure of 180&#xD;
             mmHg or more, or a diastolic blood pressure of 110 mmHg or more at primary&#xD;
             registration) or unstable angina that may worsen with the study or may affect the&#xD;
             study results based on the clinical judgment of the investigator or subinvestigator&#xD;
&#xD;
          -  Concurrence of hypotension (defined as a systolic blood pressure of less than 100 mmHg&#xD;
             at primary registration) or orthostatic hypotension&#xD;
&#xD;
          -  Concurrence of malabsorption syndrome, hepatic disease, or other conditions that may&#xD;
             affect the absorption and/or metabolism of the study drug&#xD;
&#xD;
          -  Concurrent or previous history of cerebrovascular disease or transient ischemic attack&#xD;
             (TIA)&#xD;
&#xD;
          -  Known hypersensitivity to quetiapine or any component of FK949E tablets&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Astellas Pharma Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Hokkaidou</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kantou</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kinki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=180</url>
    <description>Link to results on Astellas Clinical Study Results website</description>
  </link>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <results_first_submitted>August 14, 2014</results_first_submitted>
  <results_first_submitted_qc>August 14, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 28, 2014</results_first_posted>
  <last_update_submitted>July 19, 2019</last_update_submitted>
  <last_update_submitted_qc>July 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>patients</keyword>
  <keyword>FK949E</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quetiapine Fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.</ipd_time_frame>
    <ipd_access_criteria>Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.</ipd_access_criteria>
    <ipd_url>https://www.clinicalstudydatarequest.com/</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Quetiapine 50 mg</title>
          <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Quetiapine 150 mg</title>
          <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
        </group>
        <group group_id="P4">
          <title>Quetiapine 300 mg</title>
          <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="41"/>
                <participants group_id="P4" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="39"/>
                <participants group_id="P3" count="33"/>
                <participants group_id="P4" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Exacerbation of Target Disease</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Met Exclusion Criteria</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Site Withdrawal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Quetiapine 50 mg</title>
          <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Quetiapine 150 mg</title>
          <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
        </group>
        <group group_id="B4">
          <title>Quetiapine 300 mg</title>
          <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
        </group>
        <group group_id="B5">
          <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="44"/>
            <count group_id="B2" value="44"/>
            <count group_id="B3" value="41"/>
            <count group_id="B4" value="43"/>
            <count group_id="B5" value="172"/>
          </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="39.8" spread="11.2"/>
                    <measurement group_id="B2" value="39.0" spread="9.5"/>
                    <measurement group_id="B3" value="35.2" spread="8.6"/>
                    <measurement group_id="B4" value="37.3" spread="9.7"/>
                    <measurement group_id="B5" value="37.9" spread="9.9"/>
                  </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="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="26"/>
                    <measurement group_id="B5" value="104"/>
                  </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>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="41"/>
                    <measurement group_id="B4" value="43"/>
                    <measurement group_id="B5" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montgomery Åsberg Depression Rating Scale (MADRS)</title>
          <description>MADRS is a10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less 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="28.5" spread="5.1"/>
                    <measurement group_id="B2" value="28.7" spread="5.9"/>
                    <measurement group_id="B3" value="29.0" spread="5.4"/>
                    <measurement group_id="B4" value="29.3" spread="5.4"/>
                    <measurement group_id="B5" value="28.9" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Depression Scale 17-Item (HAM D17)</title>
          <description>HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state.</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="22.6" spread="2.3"/>
                    <measurement group_id="B2" value="22.6" spread="2.4"/>
                    <measurement group_id="B3" value="23.3" spread="3.0"/>
                    <measurement group_id="B4" value="22.9" spread="2.5"/>
                    <measurement group_id="B5" value="22.8" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</title>
        <description>The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Full Analysis Set: Participants who met the following requirements: major depressive disorder confirmed at registration; at least one dose of the study drug for the treatment period was administered; and at least one efficacy variable was assessed after the start of treatment. Last observation carried forward (LOCF) imputation was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</title>
          <description>The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.</description>
          <population>Full Analysis Set: Participants who met the following requirements: major depressive disorder confirmed at registration; at least one dose of the study drug for the treatment period was administered; and at least one efficacy variable was assessed after the start of treatment. Last observation carried forward (LOCF) imputation was used.</population>
          <units>units 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="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.5" spread="1.2"/>
                    <measurement group_id="O2" value="-11.3" spread="1.2"/>
                    <measurement group_id="O3" value="-12.1" spread="1.2"/>
                    <measurement group_id="O4" value="-10.3" spread="1.2"/>
                  </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>
            <param_type>Adjusted mean difference</param_type>
            <param_value>0.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.7</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.1</ci_lower_limit>
            <ci_upper_limit>3.6</ci_upper_limit>
            <estimate_desc>An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-0.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.7</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.0</ci_lower_limit>
            <ci_upper_limit>2.8</ci_upper_limit>
            <estimate_desc>An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted mean difference</param_type>
            <param_value>1.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.7</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.1</ci_lower_limit>
            <ci_upper_limit>4.6</ci_upper_limit>
            <estimate_desc>An analysis of covariance model with the baseline as a covariate and treatment group as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)</title>
        <description>The 17-item Hamilton Depression Scale (HAM-D17) is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 52 where a higher score indicates a greater depressive state.</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Full analysis set; Last observation carried forward (LOCF) imputation was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)</title>
          <description>The 17-item Hamilton Depression Scale (HAM-D17) is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 52 where a higher score indicates a greater depressive state.</description>
          <population>Full analysis set; Last observation carried forward (LOCF) imputation was used.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.1" spread="6.0"/>
                    <measurement group_id="O2" value="-9.3" spread="5.9"/>
                    <measurement group_id="O3" value="-10.2" spread="5.7"/>
                    <measurement group_id="O4" value="-8.7" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)</title>
        <description>The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened.&#xD;
Improvement is defined as a score of 1 or 2.</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Full analysis set; Last observation carried forward (LOCF) imputation was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)</title>
          <description>The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened.&#xD;
Improvement is defined as a score of 1 or 2.</description>
          <population>Full analysis set; Last observation carried forward (LOCF) imputation was used.</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="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.5"/>
                    <measurement group_id="O2" value="50.0"/>
                    <measurement group_id="O3" value="53.7"/>
                    <measurement group_id="O4" value="27.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)</title>
        <description>The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are:&#xD;
Limitation in physical activities because of health problems.&#xD;
Limitations in usual role activities because of physical health problems.&#xD;
Bodily pain.&#xD;
Limitations in social activities because of physical or emotional problems.&#xD;
General mental health (psychological distress and well-being).&#xD;
Limitations in usual role activities because of emotional problems.&#xD;
Vitality (energy and fatigue).&#xD;
General health perception.&#xD;
Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status.</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Full analysis set with available SF-36 data; LOCF was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)</title>
          <description>The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are:&#xD;
Limitation in physical activities because of health problems.&#xD;
Limitations in usual role activities because of physical health problems.&#xD;
Bodily pain.&#xD;
Limitations in social activities because of physical or emotional problems.&#xD;
General mental health (psychological distress and well-being).&#xD;
Limitations in usual role activities because of emotional problems.&#xD;
Vitality (energy and fatigue).&#xD;
General health perception.&#xD;
Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status.</description>
          <population>Full analysis set with available SF-36 data; LOCF was used.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="39"/>
                <count group_id="O4" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="13.3"/>
                    <measurement group_id="O2" value="1.4" spread="14.3"/>
                    <measurement group_id="O3" value="0.4" spread="14.9"/>
                    <measurement group_id="O4" value="1.4" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Limitations - Physical</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.8" spread="24.8"/>
                    <measurement group_id="O2" value="1.1" spread="28.0"/>
                    <measurement group_id="O3" value="7.4" spread="31.1"/>
                    <measurement group_id="O4" value="6.1" spread="26.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bodily pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="21.4"/>
                    <measurement group_id="O2" value="11.2" spread="23.9"/>
                    <measurement group_id="O3" value="2.5" spread="25.2"/>
                    <measurement group_id="O4" value="-0.5" spread="26.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Health Perception</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="12.3"/>
                    <measurement group_id="O2" value="6.0" spread="14.8"/>
                    <measurement group_id="O3" value="4.7" spread="16.8"/>
                    <measurement group_id="O4" value="8.7" spread="13.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vitality</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="15.8"/>
                    <measurement group_id="O2" value="8.1" spread="21.3"/>
                    <measurement group_id="O3" value="6.7" spread="15.8"/>
                    <measurement group_id="O4" value="9.2" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="21.3"/>
                    <measurement group_id="O2" value="6.5" spread="27.3"/>
                    <measurement group_id="O3" value="7.4" spread="25.9"/>
                    <measurement group_id="O4" value="6.0" spread="20.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Limitations - Emotional</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="29.5"/>
                    <measurement group_id="O2" value="13.8" spread="24.0"/>
                    <measurement group_id="O3" value="11.8" spread="27.7"/>
                    <measurement group_id="O4" value="9.7" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mental Health</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="18.9"/>
                    <measurement group_id="O2" value="9.7" spread="22.0"/>
                    <measurement group_id="O3" value="8.1" spread="16.7"/>
                    <measurement group_id="O4" value="7.5" spread="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)</title>
        <description>The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven &quot;component&quot; scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality.</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Full analysis set with available PSQI data; LOCF was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)</title>
          <description>The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven &quot;component&quot; scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality.</description>
          <population>Full analysis set with available PSQI data; LOCF was used.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="39"/>
                <count group_id="O4" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="2.9"/>
                    <measurement group_id="O2" value="-1.8" spread="2.7"/>
                    <measurement group_id="O3" value="-1.5" spread="2.7"/>
                    <measurement group_id="O4" value="-1.8" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests</title>
        <description>An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.</description>
        <time_frame>Up to 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Quetiapine 50 mg</title>
            <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Quetiapine 150 mg</title>
            <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
          </group>
          <group group_id="O4">
            <title>Quetiapine 300 mg</title>
            <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests</title>
          <description>An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="35"/>
                    <measurement group_id="O4" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related serious adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-related AE leading to discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received matching placebo tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Quetiapine 50 mg</title>
          <description>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Quetiapine 150 mg</title>
          <description>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.</description>
        </group>
        <group group_id="E4">
          <title>Quetiapine 300 mg</title>
          <description>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA/J 14.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Partial seizures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA/J 14.1</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="18" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="28" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood prolactin increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="43"/>
              </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>PI needs to get prior approval from Sponsor in writing for publication of trial data.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Vice President, Clinical Development Administration</name_or_title>
      <organization>Astellas Pharma Inc.</organization>
      <email>clinicaltrials@us.astellas.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/NCT01725282
org study id: 6949-CL-0005
nct id: NCT01725282
lead sponsor: 
has dmc: No
In this study, quetiapine XR or placebo will be administered orally for 6 weeks to major
      depressive disorder patients with lack of response to existing antidepressants, with the aim
      of evaluating the efficacy of quetiapine XR and dose-response in three quetiapine XR dose
      groups based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
time frame: Baseline and Week 6
description: The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
measure: Change From Baseline in Hamilton Rating Score for Depression (HAM-D17)
time frame: Baseline and Week 6
description: The 17-item Hamilton Depression Scale (HAM-D17) is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 52 where a higher score indicates a greater depressive state.
measure: Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I)
time frame: Baseline and Week 6
description: The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened.
Improvement is defined as a score of 1 or 2.
measure: Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
time frame: Baseline and Week 6
description: The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are:
Limitation in physical activities because of health problems.
Limitations in usual role activities because of physical health problems.
Bodily pain.
Limitations in social activities because of physical or emotional problems.
General mental health (psychological distress and well-being).
Limitations in usual role activities because of emotional problems.
Vitality (energy and fatigue).
General health perception.
Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status.
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
time frame: Baseline and Week 6
description: The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality.
measure: Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests
time frame: Up to 8 weeks
description: An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received matching placebo tablets once daily before bedtime for 7 weeks.
arm group label: Quetiapine 50 mg
arm group type: Experimental
description: Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.
arm group label: Quetiapine 150 mg
arm group type: Experimental
description: After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week.
arm group label: Quetiapine 300 mg
arm group type: Experimental
description: After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week.
intervention type: Drug
intervention name: quetiapine extended release (XR)
description: Extended release tablets
arm group label: Quetiapine 150 mg
arm group label: Quetiapine 300 mg
arm group label: Quetiapine 50 mg
other name: Seroquel XR
other name: FK949E
intervention type: Drug
intervention name: Placebo
description: matching tablets
arm group label: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 64 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Astellas Pharma Inc
facility: 
facility: 
facility: 
country: Japan
url: https://www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=180
description: Link to results on Astellas Clinical Study Results website
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Quetiapine Fumarate
sharing ipd: Yes
ipd description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
ipd access criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
ipd url: https://www.clinicalstudydatarequest.com/
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 