<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/NCT04423757</url>
  </required_header>
  <id_info>
    <org_study_id>1402-0014</org_study_id>
    <nct_id>NCT04423757</nct_id>
  </id_info>
  <brief_title>A Home-based Study Using Mobile Technology to Test Whether BI 1358894 is Effective in People With Depression</brief_title>
  <official_title>A Phase II 6-week, Randomized, Double-blinded, Placebo Controlled, Parallel Group Decentralised Clinical Trial to Evaluate Efficacy and Safety of Oral BI 1358894 in Patients With Major Depressive Disorder With Inadequate Response to Antidepressants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</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>
      This is a home-based study in adults with depression. People who have been diagnosed with&#xD;
      Major Depressive Disorder can participate in the study. Participants can take part if they&#xD;
      are being treated for their depression but still have symptoms. The purpose of this study is&#xD;
      to find out whether a medicine called BI 1358894 helps people with depression.&#xD;
&#xD;
      Participants are in the study for about 2 months and do not need to visit a study site during&#xD;
      this time. All study visits are conducted at participant's home by a mobile study nurse, by&#xD;
      videoconference, and by phone calls. Participants are put into 2 groups by chance. One group&#xD;
      takes BI 1358894 tablets. The other group takes placebo tablets. Placebo tablets look like BI&#xD;
      1358894 tablets but do not contain any medicine.&#xD;
&#xD;
      The participants answer questions about the symptoms of their depression. We then compare the&#xD;
      results between the BI 1358894 and placebo groups. The doctors and nurses also regularly&#xD;
      check the general health of the participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment challenges&#xD;
  </why_stopped>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Actual">May 8, 2022</completion_date>
  <primary_completion_date type="Actual">April 19, 2022</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in MADRS Total Score at Week 6</measure>
    <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
    <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). The adjusted mean (SE) are based on a mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6</measure>
    <time_frame>Baseline (week 0) and after 6 weeks of treatment.</time_frame>
    <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). Reported are the number of subjects with ≥ 50% MADRS reduction from baseline at Weeks 6. Percent reduction from baseline was calculated as (score at baseline - score at week 6) / score at baseline * 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6</measure>
    <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
    <description>The State-Trait Anxiety Inventory (STAI) comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel &quot;right now, at this moment.&quot; The T-Anxiety scale consists of twenty statements that assess how people generally feel. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6</measure>
    <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
    <description>The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited, taking into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 (best) to 7 (worst). Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. MMRM with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6</measure>
    <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
    <description>The SMDDS is a 16-item, patient-reported outcome (PRO) measure developed to capture the core symptoms of MDD. The SMDDS uses a recall of &quot;over the past 7 days&quot; and participants respond to each question using a rating scale between 0 (&quot;Not at all&quot; or &quot;Never&quot;) to 4 (&quot;Extremely&quot; or &quot;Always&quot;). In calculating the total score, two of the items (item 11 and 12) are first combined, with the highest score across the two items selected for use in the total score calculation. Total score is then calculated by the sum of the individual 15 items, the total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6</measure>
    <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
    <description>The PGI-S was used to measure the patient's impression of the severity of their illness. It is a single item 4-point scale that asks patients to rate the severity of their illness.&#xD;
The PGI-S question states &quot;Please choose the response below that best describes the overall severity of your depression symptoms over the past week.&quot;&#xD;
None&#xD;
Mild&#xD;
Moderate&#xD;
Severe&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change Scale (PGI-C) Score at Week 6</measure>
    <time_frame>After 6 weeks of treatment.</time_frame>
    <description>The PGI-C is a one-time assessment at the end of treatment (EoT) to measure the patient's impression of the how their illness has changed over time. It is a single item 7-item scale that asks patients to rate the overall change since the start of treatment.&#xD;
The PGI-C question states &quot;Please choose the response below that best describes the overall change in your depression symptoms since you started taking the study medication.&quot;&#xD;
Very much improved&#xD;
Much improved&#xD;
Minimally improved&#xD;
No change&#xD;
Minimally worse&#xD;
Much worse&#xD;
Very much worse</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>BI 1358894</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1358894</intervention_name>
    <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
    <arm_group_label>BI 1358894</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Established diagnosis of Major Depressive Disorder, single episode or recurrent, as&#xD;
             confirmed at the time of screening by the Structured Clinical Interview for Diagnostic&#xD;
             and Statistical Manual of Mental Disorders v5 (DSM-5, SCID-5), with a duration of&#xD;
             current depressive episode ≥ 8 weeks and ≤ 12 months at the time of screening visit.&#xD;
&#xD;
          -  Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 22 at screening, as&#xD;
             confirmed by a trained rater. In addition, trial participants must have a score of ≥ 3&#xD;
             on the Reported Sadness item on MADRS.&#xD;
&#xD;
          -  A documented ongoing monotherapy treatment of ≥ 8 weeks at the screening visit, with a&#xD;
             protocol specified SSRI or SNRI (refer to the ISF) at adequate dose (at least minimum&#xD;
             effective dose as per prescribing information and as confirmed per detectable drug&#xD;
             levels in the screening blood or urine sampling).&#xD;
&#xD;
          -  Male and female participants, 18 to 65 years of age, both inclusively at the time of&#xD;
             consent.&#xD;
&#xD;
          -  Women of child-bearing potential (WOCBP)2 able and willing to use two methods of&#xD;
             contraception, which include one highly effective method of birth control per ICH M3&#xD;
             (R2) that results in a low failure rate of less than 1%, plus one barrier method.&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with ICH-GCP and local&#xD;
             legislation prior to admission to the trial.&#xD;
&#xD;
          -  Able to communicate well, and to understand and comply with trial requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective&#xD;
             disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with&#xD;
             psychotic features as assessed by the Structured Clinical Interview for DSM -5&#xD;
             (SCID-5) at the time of screening.&#xD;
&#xD;
          -  Diagnosis of any other mental disorder (in addition to those as described in Exclusion&#xD;
             Criterion #1) that was the primary focus of treatment within 6 months prior to&#xD;
             screening or at baseline (as per clinical discretion of the investigator).&#xD;
&#xD;
          -  Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as&#xD;
             per DSM-5 criteria, at the time of screening visit. Any other personality disorder at&#xD;
             screening visit that significantly affects current psychiatric status and likely to&#xD;
             impact trial participation, as per the judgement of investigator.&#xD;
&#xD;
          -  Diagnosis of a substance related disorder within 3 months prior to screening visit&#xD;
             (with exception of caffeine and tobacco).&#xD;
&#xD;
          -  History of seizure disorders, stroke, brain tumor or any other major neurological&#xD;
             illness that can impact participation in the trial.&#xD;
&#xD;
          -  History of 4 or more unsuccessful monotherapy treatments (at adequate dosage and&#xD;
             duration, per local prescribing information of the product) with an approved&#xD;
             antidepressant medication for the current ongoing major depressive episode. These&#xD;
             include ongoing monotherapy treatment with a protocol specified SSRI or SNRI as&#xD;
             described in Inclusion Criterion #3.&#xD;
&#xD;
          -  Any suicidal behavior in the past 12 months prior to screening (per investigator&#xD;
             judgement including an actual attempt, interrupted attempt, aborted attempt, or&#xD;
             preparatory acts or behaviour).&#xD;
&#xD;
          -  Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale&#xD;
             (CSSRS) in the past 3 months prior to screening or at screening or baseline visit&#xD;
             (i.e. active suicidal thought with method and intent but without specific plan, or&#xD;
             active suicidal thought with method, intent and plan).&#xD;
&#xD;
          -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Science 37, Inc.</name>
      <address>
        <city>Culver City</city>
        <state>California</state>
        <zip>90230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <results_first_submitted>April 18, 2023</results_first_submitted>
  <results_first_submitted_qc>April 18, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 11, 2023</results_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</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>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed &quot;Document Sharing Agreement&quot;.&#xD;
Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.&#xD;
The data shared are the raw clinical study data sets.</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>After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.</ipd_access_criteria>
    <ipd_url>https://www.mystudywindow.com/msw/datasharing</ipd_url>
  </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>July 20, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT04423757/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>July 1, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT04423757/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted as a decentralized clinical trial (DCT). It was a 6-week parallel-group, randomized, double-blinded, placebo-controlled Phase II trial in participants with Major Depressive Disorder (MDD) with inadequate response to ongoing treatment of an Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin and Norepinephrine Reuptake Inhibitor (SNRI).</recruitment_details>
      <pre_assignment_details>All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 1358894</title>
          <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 1358894</title>
          <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="43"/>
          </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="41.1" spread="13.4"/>
                    <measurement group_id="B2" value="43.2" spread="13.0"/>
                    <measurement group_id="B3" value="42.2" spread="13.1"/>
                  </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="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montgomery-Åsberg Depression Rating Scale (MADRS)</title>
          <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). Baseline for MADRS is last measurement prior to treatment start.</description>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.6" spread="6.6"/>
                    <measurement group_id="B2" value="28.4" spread="7.1"/>
                    <measurement group_id="B3" value="27.6" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in MADRS Total Score at Week 6</title>
        <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). The adjusted mean (SE) are based on a mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect.</description>
        <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in MADRS Total Score at Week 6</title>
          <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). The adjusted mean (SE) are based on a mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</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="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.98" spread="NA">Adjusted standard error = 2.3</measurement>
                    <measurement group_id="O2" value="-13.36" spread="NA">Adjusted standard error = 2.0</measurement>
                  </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>
            <groups_desc>Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2796</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>3.38</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.81</ci_lower_limit>
            <ci_upper_limit>8.56</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6</title>
        <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). Reported are the number of subjects with ≥ 50% MADRS reduction from baseline at Weeks 6. Percent reduction from baseline was calculated as (score at baseline - score at week 6) / score at baseline * 100.</description>
        <time_frame>Baseline (week 0) and after 6 weeks of treatment.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6</title>
          <description>The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). Reported are the number of subjects with ≥ 50% MADRS reduction from baseline at Weeks 6. Percent reduction from baseline was calculated as (score at baseline - score at week 6) / score at baseline * 100.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="14"/>
                  </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>
            <groups_desc>Logistic regression includes treatment as covariate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0468</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.276</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.091</ci_lower_limit>
            <ci_upper_limit>0.781</ci_upper_limit>
            <estimate_desc>For the calculation of the odds ratio Placebo is taken as reference.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6</title>
        <description>The State-Trait Anxiety Inventory (STAI) comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel &quot;right now, at this moment.&quot; The T-Anxiety scale consists of twenty statements that assess how people generally feel. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
        <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint. One subject in the BI 1358894 arm missed the baseline assessment for STAI and was excluded from this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6</title>
          <description>The State-Trait Anxiety Inventory (STAI) comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel &quot;right now, at this moment.&quot; The T-Anxiety scale consists of twenty statements that assess how people generally feel. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint. One subject in the BI 1358894 arm missed the baseline assessment for STAI and was excluded from this endpoint.</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="19"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>S-Anxiety scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.10" spread="NA">Adjusted standard error = 2.6</measurement>
                    <measurement group_id="O2" value="-10.45" spread="NA">Adjusted standard error = 2.3</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T-Anxiety scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.70" spread="NA">Adjusted standard error = 2.3</measurement>
                    <measurement group_id="O2" value="-12.24" spread="NA">Adjusted standard error = 2.0</measurement>
                  </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>
            <groups_desc>S-Anxiety scale - Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.6980</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>1.35</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.5</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.47</ci_lower_limit>
            <ci_upper_limit>7.17</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>T-Anxiety scale - Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2589</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>3.54</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.67</ci_lower_limit>
            <ci_upper_limit>8.76</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6</title>
        <description>The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited, taking into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 (best) to 7 (worst). Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. MMRM with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
        <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6</title>
          <description>The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited, taking into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 (best) to 7 (worst). Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. MMRM with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</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="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.14" spread="NA">Adjusted standard error = 0.3</measurement>
                    <measurement group_id="O2" value="-1.65" spread="NA">Adjusted standard error = 0.3</measurement>
                  </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>
            <groups_desc>Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1863</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>0.51</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.13</ci_lower_limit>
            <ci_upper_limit>1.15</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6</title>
        <description>The SMDDS is a 16-item, patient-reported outcome (PRO) measure developed to capture the core symptoms of MDD. The SMDDS uses a recall of &quot;over the past 7 days&quot; and participants respond to each question using a rating scale between 0 (&quot;Not at all&quot; or &quot;Never&quot;) to 4 (&quot;Extremely&quot; or &quot;Always&quot;). In calculating the total score, two of the items (item 11 and 12) are first combined, with the highest score across the two items selected for use in the total score calculation. Total score is then calculated by the sum of the individual 15 items, the total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
        <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6</title>
          <description>The SMDDS is a 16-item, patient-reported outcome (PRO) measure developed to capture the core symptoms of MDD. The SMDDS uses a recall of &quot;over the past 7 days&quot; and participants respond to each question using a rating scale between 0 (&quot;Not at all&quot; or &quot;Never&quot;) to 4 (&quot;Extremely&quot; or &quot;Always&quot;). In calculating the total score, two of the items (item 11 and 12) are first combined, with the highest score across the two items selected for use in the total score calculation. Total score is then calculated by the sum of the individual 15 items, the total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</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="19"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.56" spread="NA">Adjusted standard error = 2.3</measurement>
                    <measurement group_id="O2" value="-14.21" spread="NA">Adjusted standard error = 2.0</measurement>
                  </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>
            <groups_desc>Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.8326</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>0.65</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.46</ci_lower_limit>
            <ci_upper_limit>5.76</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6</title>
        <description>The PGI-S was used to measure the patient's impression of the severity of their illness. It is a single item 4-point scale that asks patients to rate the severity of their illness.&#xD;
The PGI-S question states &quot;Please choose the response below that best describes the overall severity of your depression symptoms over the past week.&quot;&#xD;
None&#xD;
Mild&#xD;
Moderate&#xD;
Severe&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
        <time_frame>Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6</title>
          <description>The PGI-S was used to measure the patient's impression of the severity of their illness. It is a single item 4-point scale that asks patients to rate the severity of their illness.&#xD;
The PGI-S question states &quot;Please choose the response below that best describes the overall severity of your depression symptoms over the past week.&quot;&#xD;
None&#xD;
Mild&#xD;
Moderate&#xD;
Severe&#xD;
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</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="11"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.37" spread="NA">Adjusted standard error = 0.3</measurement>
                    <measurement group_id="O2" value="-0.60" spread="NA">Adjusted standard error = 0.2</measurement>
                  </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>
            <groups_desc>Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.5567</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>0.23</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.43</ci_lower_limit>
            <ci_upper_limit>0.89</ci_upper_limit>
            <estimate_desc>Difference calculated as BI - Placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change Scale (PGI-C) Score at Week 6</title>
        <description>The PGI-C is a one-time assessment at the end of treatment (EoT) to measure the patient's impression of the how their illness has changed over time. It is a single item 7-item scale that asks patients to rate the overall change since the start of treatment.&#xD;
The PGI-C question states &quot;Please choose the response below that best describes the overall change in your depression symptoms since you started taking the study medication.&quot;&#xD;
Very much improved&#xD;
Much improved&#xD;
Minimally improved&#xD;
No change&#xD;
Minimally worse&#xD;
Much worse&#xD;
Very much worse</description>
        <time_frame>After 6 weeks of treatment.</time_frame>
        <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1358894</title>
            <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change Scale (PGI-C) Score at Week 6</title>
          <description>The PGI-C is a one-time assessment at the end of treatment (EoT) to measure the patient's impression of the how their illness has changed over time. It is a single item 7-item scale that asks patients to rate the overall change since the start of treatment.&#xD;
The PGI-C question states &quot;Please choose the response below that best describes the overall change in your depression symptoms since you started taking the study medication.&quot;&#xD;
Very much improved&#xD;
Much improved&#xD;
Minimally improved&#xD;
No change&#xD;
Minimally worse&#xD;
Much worse&#xD;
Very much worse</description>
          <population>Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.</population>
          <units>Score 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="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="1.1"/>
                    <measurement group_id="O2" value="2.8" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days.</time_frame>
      <desc>Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 1358894</title>
          <description>125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.0</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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 25.0</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="14" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Feeling abnormal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </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>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Results should be interpreted in a descriptive manner since the trial was terminated early and the specified number of patients required for the analyses was not obtained.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim , Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.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/NCT04423757
org study id: 1402-0014
nct id: NCT04423757
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a home-based study in adults with depression. People who have been diagnosed with
      Major Depressive Disorder can participate in the study. Participants can take part if they
      are being treated for their depression but still have symptoms. The purpose of this study is
      to find out whether a medicine called BI 1358894 helps people with depression.

      Participants are in the study for about 2 months and do not need to visit a study site during
      this time. All study visits are conducted at participant's home by a mobile study nurse, by
      videoconference, and by phone calls. Participants are put into 2 groups by chance. One group
      takes BI 1358894 tablets. The other group takes placebo tablets. Placebo tablets look like BI
      1358894 tablets but do not contain any medicine.

      The participants answer questions about the symptoms of their depression. We then compare the
      results between the BI 1358894 and placebo groups. The doctors and nurses also regularly
      check the general health of the participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline in MADRS Total Score at Week 6
time frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
description: The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). The adjusted mean (SE) are based on a mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect.
measure: Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6
time frame: Baseline (week 0) and after 6 weeks of treatment.
description: The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). Reported are the number of subjects with ≥ 50% MADRS reduction from baseline at Weeks 6. Percent reduction from baseline was calculated as (score at baseline - score at week 6) / score at baseline * 100.
measure: Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6
time frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
description: The State-Trait Anxiety Inventory (STAI) comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel "right now, at this moment." The T-Anxiety scale consists of twenty statements that assess how people generally feel. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
measure: Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6
time frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
description: The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited, taking into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 (best) to 7 (worst). Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. MMRM with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
measure: Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6
time frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
description: The SMDDS is a 16-item, patient-reported outcome (PRO) measure developed to capture the core symptoms of MDD. The SMDDS uses a recall of "over the past 7 days" and participants respond to each question using a rating scale between 0 ("Not at all" or "Never") to 4 ("Extremely" or "Always"). In calculating the total score, two of the items (item 11 and 12) are first combined, with the highest score across the two items selected for use in the total score calculation. Total score is then calculated by the sum of the individual 15 items, the total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
measure: Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6
time frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
description: The PGI-S was used to measure the patient's impression of the severity of their illness. It is a single item 4-point scale that asks patients to rate the severity of their illness.
The PGI-S question states "Please choose the response below that best describes the overall severity of your depression symptoms over the past week."
None
Mild
Moderate
Severe
Mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
measure: Patient Global Impression of Change Scale (PGI-C) Score at Week 6
time frame: After 6 weeks of treatment.
description: The PGI-C is a one-time assessment at the end of treatment (EoT) to measure the patient's impression of the how their illness has changed over time. It is a single item 7-item scale that asks patients to rate the overall change since the start of treatment.
The PGI-C question states "Please choose the response below that best describes the overall change in your depression symptoms since you started taking the study medication."
Very much improved
Much improved
Minimally improved
No change
Minimally worse
Much worse
Very much worse
arm group label: BI 1358894
arm group type: Experimental
description: 125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
intervention type: Drug
intervention name: BI 1358894
description: 125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.
arm group label: BI 1358894
intervention type: Drug
intervention name: Placebo
description: Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: Yes
ipd description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".
Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
The data shared are the raw clinical study data sets.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
ipd access criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
ipd url: https://www.mystudywindow.com/msw/datasharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Results should be interpreted in a descriptive manner since the trial was terminated early and the specified number of patients required for the analyses was not obtained.
point of contact: 