<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/NCT03230097</url>
  </required_header>
  <id_info>
    <org_study_id>1289.32</org_study_id>
    <secondary_id>2016-004973-42</secondary_id>
    <nct_id>NCT03230097</nct_id>
  </id_info>
  <brief_title>This Study Tests Whether BI 409306 Prevents Patients With a Specific Type of Mental Illness (Attenuated Psychosis Syndrome) From Becoming Worse. This Study Looks at How Well Patients Tolerate the Medicine and How Effective it is Over 1 Year</brief_title>
  <official_title>A Phase II Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered BI 409306 During a 52-week Treatment Period as an Early Intervention in Patients With Attenuated Psychosis Syndrome.</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>Yes</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 study in people between 16 and 30 years of age who have a specific type of mental&#xD;
      illness called attenuated psychosis syndrome (APS). The purpose of this study is to find out&#xD;
      whether BI 409306 helps reduce the symptoms of APS.&#xD;
&#xD;
      Participants are in the study for 1 year and 2 months. During this time, they visit the study&#xD;
      site about 15 times and get about 10 phone calls. Participants are put into 2 groups by&#xD;
      chance. They get either BI 409306 or placebo. Placebo tablets look like BI 409306 tablets but&#xD;
      do not contain any medicine. Participants take a BI 409306 or placebo tablet two times a day.&#xD;
&#xD;
      During the study, participants answer questions in interviews and complete questionnaires so&#xD;
      the doctors can check whether the APS symptoms change. The doctors also check the general&#xD;
      health of the participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    disruption due to COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">September 29, 2017</start_date>
  <completion_date type="Actual">April 7, 2021</completion_date>
  <primary_completion_date type="Actual">March 17, 2021</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>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe</measure>
    <time_frame>Up to 52 weeks.</time_frame>
    <description>Incidence of remission from attenuated psychosis syndrome (APS) within a 52-week timeframe. The incidence rate per patient-years of remission from attenuated psychosis syndrome (APS) is reported. Remission from APS is defined as a score of &lt;3 on all of the five Positive Symptom items of the Scale of Prodromal Symptoms (SOPS) and maintained until the end of treatment. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms. incidence rate = number of events/total time at risk [patient-years].</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of First Episode of Psychosis</measure>
    <time_frame>Up to 52 weeks.</time_frame>
    <description>Incidence of first episode of psychosis. The incidence rate per patient-years of psychosis is reported, psychosis is defined as one or more positive Scale of Prodromal Symptoms (SOPS) symptoms rated a 6 AND either a symptom is seriously disorganizing or dangerous OR one of the symptoms above occurred at least one hour per day at an average frequency of four days/week over the past month. OR a new prescription or increase in dose of an ongoing antipsychotic medication. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment</measure>
    <time_frame>Baseline, week 24 and week 52.</time_frame>
    <description>Change from baseline (Day -28 to -7) in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 24 and 52 weeks of treatment. 20-item assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80). Data analyzed using the restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment</measure>
    <time_frame>Baseline and week 52.</time_frame>
    <description>Change from baseline (Day -28 to -7) in the tablet based Brief Assessment of Cognition (BAC App) composite T score after 52 weeks of treatment. The BAC consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores was generated (averages five of the standardized scaled sub-test scores, token motor test score not included), larger T-score indicates better cognition. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction. T-scores in the general population have a mean of 50 and standard deviation of 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment</measure>
    <time_frame>Baseline and week 52.</time_frame>
    <description>Change from baseline (Day -28 to -7) in Positive and Negative Syndrome Scale (PANSS) positive items score, negative items score, and total score after 52 weeks of treatment. The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline NAPLS risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Psychotic Disorders</condition>
  <arm_group>
    <arm_group_label>BI 409306</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 409306</intervention_name>
    <description>50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
    <arm_group_label>BI 409306</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Meet diagnostic criteria for attenuated psychosis syndrome as defined in DSM-5 and&#xD;
             determined by SIPS administered at screening and diagnosis confirmed by NeuroCog&#xD;
             Trials after review of video-taped SIPS interview.&#xD;
&#xD;
          -  Age ≥16 and ≤ 30 years at the time of consent/assent.&#xD;
&#xD;
          -  Male or female patients willing to use highly effective methods of contraception.&#xD;
&#xD;
               -  Female patients of childbearing potential must be ready and able to use highly&#xD;
                  effective methods of birth control per ICH M3 (R2) that result in a low failure&#xD;
                  rate of less than 1% per year when used consistently and correctly. Patients must&#xD;
                  agree to use birth control throughout the trial and for at least 28 days after&#xD;
                  treatment has ended. Acceptable methods of birth control include combined&#xD;
                  estrogen-progestin oral, intravaginal or transdermal contraceptives,&#xD;
                  progestogen-only oral, injectable or implantable contraceptives, intrauterine&#xD;
                  devices (IUDs), intrauterine hormone releasing systems (IUSs), bilateral tubal&#xD;
                  occlusion, vasectomized sexual partner, and complete sexual abstinence (if&#xD;
                  acceptable by local health authorities) is allowed when this is in line with the&#xD;
                  preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,&#xD;
                  calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are&#xD;
                  not acceptable methods of contraception.&#xD;
&#xD;
               -  Male patients who are able to father a child must be ready and able to be&#xD;
                  abstinent or use adequate contraception for the duration of study participation&#xD;
                  and for at least 28 days after treatment has ended.&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with Good Clinical Practice&#xD;
             (GCP) and local legislation prior to any study-related procedures OR signed and dated&#xD;
             informed consent provided by the patient's parent(s) (or legal guardian) and assent by&#xD;
             the patient prior to any study-related procedures in accordance with GCP and local&#xD;
             legislation. If the patient has a legal representative, then this legal representative&#xD;
             must give written informed consent as well.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Present or past diagnosis of schizophrenia, schizophreniform, schizoaffective&#xD;
             disorder, bipolar disorder I, major depressive disorder with psychotic features,&#xD;
             delusional disorder, brief psychotic disorder, other specified schizophrenia spectrum&#xD;
             and other psychotic disorder (except attenuated psychosis syndrome), and unspecified&#xD;
             schizophrenia spectrum and other psychotic disorder, according to DSM-5.&#xD;
&#xD;
          -  Patients taking antipsychotic medication for less than 8 weeks, or patients taking&#xD;
             antipsychotic medication for a longer duration but who have not been on a stable dose&#xD;
             for 8 weeks prior to informed consent.&#xD;
&#xD;
          -  Patients who begin taking an antipsychotic between Visit 1 and Visit 2.&#xD;
&#xD;
          -  Patients who have discontinued an antipsychotic medication less than two weeks prior&#xD;
             to randomization.&#xD;
&#xD;
          -  Patients taking Clozapine.&#xD;
&#xD;
          -  Suicidal behavior in the past 2 years reported in the Columbia Suicide Severity Rating&#xD;
             Scale (C-SSRS) with a lethality of attempt ≥1, or with a lethality of 0 but a&#xD;
             potential lethality of 2, or that in the judgement of the investigator would&#xD;
             jeopardize the patient's safety while participating in the trial. The&#xD;
             investigator/qualified rater must review all screening C-SSRS reports prior to&#xD;
             randomization, documenting an additional interview assessing lethality of the behavior&#xD;
             history when appropriate.&#xD;
&#xD;
          -  Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale&#xD;
             (CSSRS) in the past 3 months (i.e. active suicidal thought with intent but without&#xD;
             specific plan, or active suicidal thought with plan and intent).&#xD;
&#xD;
          -  In the judgment of the investigator, any clinically significant finding from the&#xD;
             physical examination or laboratory value deviating from normal or any evidence of a&#xD;
             clinically significant concomitant disease or any other clinical condition that would&#xD;
             jeopardize a patient's safety while participating in the clinical trial.&#xD;
&#xD;
          -  Known diseases of the central nervous system (including but not limited to any kind of&#xD;
             seizures or stroke).&#xD;
&#xD;
          -  History of significant head injury (&gt;5 minutes without consciousness).&#xD;
&#xD;
          -  A serious developmental disorder that in the judgement of the investigator would&#xD;
             inhibit the patient's ability to comply with all study procedures, or mental&#xD;
             retardation (documented IQ &lt;70), or acute attenuated symptoms exclusively related to&#xD;
             intoxication from a psychotropic substance.&#xD;
&#xD;
          -  Any documented active or suspected malignancy or history of malignancy within 5 years&#xD;
             prior to screening, except appropriately treated basal cell carcinoma of the skin or&#xD;
             in situ carcinoma of uterine cervix.&#xD;
&#xD;
          -  Planned elective surgery requiring general anesthesia, or hospitalization for more&#xD;
             than 1 day during the study period.&#xD;
&#xD;
          -  Meets criteria for Substance Use Disorder (DSM-5) within the six months prior to&#xD;
             informed consent/assent.&#xD;
&#xD;
          -  Patients who must or wish to continue the intake of restricted medications or any drug&#xD;
             considered likely to interfere with the safe conduct of the trial.&#xD;
&#xD;
          -  Patients taking strong or moderate CYP1A2 inhibitors who are also a CYP2C19 Poor&#xD;
             Metabolizer (PM). Patients taking medication known to be a strong or moderate&#xD;
             inhibitor of CYP1A2 must be prospectively genotyped to ensure they are not poor&#xD;
             metabolizers of CYP2C19. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the&#xD;
             ISF.).&#xD;
&#xD;
          -  Patients taking strong or moderate CYP1A2 inhibitors who are also taking concomitant&#xD;
             strong or moderate CYP2C19 inhibitors. (A list of CYP1A2 and CYP2C19 inhibitors can be&#xD;
             found in the ISF.)&#xD;
&#xD;
          -  Patients with a history of moderate to severe hepatic impairment (Child-Pugh B / C).&#xD;
&#xD;
          -  Patients with a history of moderate to severe renal impairment (Stage 3 - 5).&#xD;
&#xD;
          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial.&#xD;
&#xD;
          -  In the judgment of the investigator, inability of the patient to comply with the&#xD;
             clinical trial procedures.&#xD;
&#xD;
          -  Currently enrolled in another investigational device or drug study, or less than 30&#xD;
             days since ending another investigational device or drug study(s), or receiving other&#xD;
             investigational treatment(s).&#xD;
&#xD;
          -  Previous participation in any BI 409306 study.&#xD;
&#xD;
          -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ProScience Research Group</name>
      <address>
        <city>Culver City</city>
        <state>California</state>
        <zip>90230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PRIME Clinic</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Group of Central Florida</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Clinical Research Institute PC</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cherry Health</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Precise Research Centers</name>
      <address>
        <city>Flowood</city>
        <state>Mississippi</state>
        <zip>39232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altea Research Institute</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center For Emotional Fitness</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Finger Lakes Clinical Research</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth Medical Group</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Clinical Research, Inc.</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78754</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hills Clinical Research</name>
      <address>
        <city>Irving</city>
        <state>Texas</state>
        <zip>75062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychiatric and Behavioral Solutions, LLC</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital (University of Alberta)</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chatham-Kent Clinical Trials Research Centre</name>
      <address>
        <city>Chatham</city>
        <state>Ontario</state>
        <zip>N7L 1C1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alan D. Lowe Medicine Professional Corporation</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>L3R 1A3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Sixth Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100089</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Mental Health Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holywell Hospital</name>
      <address>
        <city>Antrim</city>
        <zip>BT41 2RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Barberry National Centre for Mental Health</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <zip>SE5 8AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manchester</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9PL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>China</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <results_first_submitted>March 14, 2022</results_first_submitted>
  <results_first_submitted_qc>June 3, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 29, 2022</results_first_posted>
  <last_update_submitted>June 3, 2022</last_update_submitted>
  <last_update_submitted_qc>June 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>BI 409306</mesh_term>
  </intervention_browse>
  <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>October 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT03230097/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>May 21, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT03230097/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a randomised, placebo-controlled, double-blind, parallel group trial over 52 weeks. The patients were randomised to 1 of the 2 treatment groups at a ratio of 1:1. After completion of the treatment period, or following early discontinuation, patients were to complete a 4-weeks follow-up period.</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 409306</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 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="24"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Trial termination</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Covid-19 pandemic outbreak</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>outcome event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 409306</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 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="24"/>
            <count group_id="B2" value="26"/>
            <count group_id="B3" value="50"/>
          </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="23.4" spread="4"/>
                    <measurement group_id="B2" value="20.9" spread="3.8"/>
                    <measurement group_id="B3" value="22.1" spread="4"/>
                  </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="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </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="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="43"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </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="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Schizophrenia Cognition Rating Scale (SCoRS) total score</title>
          <description>Schizophrenia Cognition Rating Scale (SCoRS) total score. The SCoRS is a 20-item interview-based assessment of cognitive deficits and the degree to which they affect day-to-day functions. It collects information from a patient interview, interview with an informant (if available), and the administering clinician. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80).</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="36.333" spread="7.405"/>
                    <measurement group_id="B2" value="36.462" spread="7.814"/>
                    <measurement group_id="B3" value="36.400" spread="7.543"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Brief Assessment of Cognition (BAC App) composite T score</title>
          <description>Brief Assessment of Cognition (BAC App) composite T score (averages five of the standardized scaled sub-test scores, token motor test score not included). The BACS consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores will be generated, larger T-score indicates better cognition. T-scores in the general population have a mean of 50 and standard deviation of 10.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52.417" spread="7.945"/>
                    <measurement group_id="B2" value="49.308" spread="13.451"/>
                    <measurement group_id="B3" value="50.800" spread="11.154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Positive and Negative Syndrome Scale (PANSS)</title>
          <description>The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms.</description>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Positive scale subtotal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.0" spread="3.9"/>
                    <measurement group_id="B2" value="14.5" spread="3.4"/>
                    <measurement group_id="B3" value="15.2" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative scale subtotal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.4" spread="5.1"/>
                    <measurement group_id="B2" value="13.4" spread="3.3"/>
                    <measurement group_id="B3" value="13.9" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.8" spread="12.5"/>
                    <measurement group_id="B2" value="58.2" spread="11.0"/>
                    <measurement group_id="B3" value="60.4" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe</title>
        <description>Incidence of remission from attenuated psychosis syndrome (APS) within a 52-week timeframe. The incidence rate per patient-years of remission from attenuated psychosis syndrome (APS) is reported. Remission from APS is defined as a score of &lt;3 on all of the five Positive Symptom items of the Scale of Prodromal Symptoms (SOPS) and maintained until the end of treatment. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms. incidence rate = number of events/total time at risk [patient-years].</description>
        <time_frame>Up to 52 weeks.</time_frame>
        <population>Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe</title>
          <description>Incidence of remission from attenuated psychosis syndrome (APS) within a 52-week timeframe. The incidence rate per patient-years of remission from attenuated psychosis syndrome (APS) is reported. Remission from APS is defined as a score of &lt;3 on all of the five Positive Symptom items of the Scale of Prodromal Symptoms (SOPS) and maintained until the end of treatment. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms. incidence rate = number of events/total time at risk [patient-years].</description>
          <population>Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.</population>
          <units>remissions per patient-years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.433"/>
                    <measurement group_id="O2" value="0.446"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.7873</p_value>
            <method>Regression, Cox</method>
            <method_desc>Stratified (by baseline use of antipsychotic medication) Cox proportional hazards model was used. Treatment effect and NAPLS risk score as covariates.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.849</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.258</ci_lower_limit>
            <ci_upper_limit>2.795</ci_upper_limit>
            <estimate_desc>Ratio = BI 409306/placebo.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of First Episode of Psychosis</title>
        <description>Incidence of first episode of psychosis. The incidence rate per patient-years of psychosis is reported, psychosis is defined as one or more positive Scale of Prodromal Symptoms (SOPS) symptoms rated a 6 AND either a symptom is seriously disorganizing or dangerous OR one of the symptoms above occurred at least one hour per day at an average frequency of four days/week over the past month. OR a new prescription or increase in dose of an ongoing antipsychotic medication. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms.</description>
        <time_frame>Up to 52 weeks.</time_frame>
        <population>Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of First Episode of Psychosis</title>
          <description>Incidence of first episode of psychosis. The incidence rate per patient-years of psychosis is reported, psychosis is defined as one or more positive Scale of Prodromal Symptoms (SOPS) symptoms rated a 6 AND either a symptom is seriously disorganizing or dangerous OR one of the symptoms above occurred at least one hour per day at an average frequency of four days/week over the past month. OR a new prescription or increase in dose of an ongoing antipsychotic medication. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms.</description>
          <population>Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.</population>
          <units>first episodes per patient-years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0.125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment</title>
        <description>Change from baseline (Day -28 to -7) in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 24 and 52 weeks of treatment. 20-item assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80). Data analyzed using the restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
        <time_frame>Baseline, week 24 and week 52.</time_frame>
        <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment</title>
          <description>Change from baseline (Day -28 to -7) in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 24 and 52 weeks of treatment. 20-item assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80). Data analyzed using the restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
          <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted mean change from baseline at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.12" lower_limit="-7.721" upper_limit="3.484"/>
                    <measurement group_id="O2" value="-3.89" lower_limit="-8.925" upper_limit="1.148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted mean change from baseline at week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.05" lower_limit="-8.881" upper_limit="2.778"/>
                    <measurement group_id="O2" value="-6.23" lower_limit="-11.530" upper_limit="-0.927"/>
                  </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>BI 409306 vs. placebo of change from baseline at week 24. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.5212</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>1.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.773</ci_lower_limit>
            <ci_upper_limit>7.315</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>BI 409306 vs. placebo of change from baseline at week 52. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.3127</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>3.18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.071</ci_lower_limit>
            <ci_upper_limit>9.425</ci_upper_limit>
            <estimate_desc>Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM), see endpoint description for details.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment</title>
        <description>Change from baseline (Day -28 to -7) in the tablet based Brief Assessment of Cognition (BAC App) composite T score after 52 weeks of treatment. The BAC consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores was generated (averages five of the standardized scaled sub-test scores, token motor test score not included), larger T-score indicates better cognition. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction. T-scores in the general population have a mean of 50 and standard deviation of 10.</description>
        <time_frame>Baseline and week 52.</time_frame>
        <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment</title>
          <description>Change from baseline (Day -28 to -7) in the tablet based Brief Assessment of Cognition (BAC App) composite T score after 52 weeks of treatment. The BAC consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores was generated (averages five of the standardized scaled sub-test scores, token motor test score not included), larger T-score indicates better cognition. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction. T-scores in the general population have a mean of 50 and standard deviation of 10.</description>
          <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
          <units>T-score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.51" lower_limit="-7.950" upper_limit="4.929"/>
                    <measurement group_id="O2" value="3.48" lower_limit="-1.641" upper_limit="8.597"/>
                  </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>BI 409306 vs. placebo of change from baseline at week 52. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1602</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-4.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.033</ci_lower_limit>
            <ci_upper_limit>2.057</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment</title>
        <description>Change from baseline (Day -28 to -7) in Positive and Negative Syndrome Scale (PANSS) positive items score, negative items score, and total score after 52 weeks of treatment. The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline NAPLS risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
        <time_frame>Baseline and week 52.</time_frame>
        <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment</title>
          <description>Change from baseline (Day -28 to -7) in Positive and Negative Syndrome Scale (PANSS) positive items score, negative items score, and total score after 52 weeks of treatment. The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline NAPLS risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</description>
          <population>All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted mean change from baseline at week 52, positive items score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.83" lower_limit="-6.355" upper_limit="-1.296"/>
                    <measurement group_id="O2" value="-3.03" lower_limit="-5.312" upper_limit="-0.743"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted mean change from baseline at week 52, negative items score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.98" lower_limit="-3.571" upper_limit="1.609"/>
                    <measurement group_id="O2" value="-2.41" lower_limit="-4.788" upper_limit="-0.032"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted mean change from baseline at week 52, total score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.02" lower_limit="-14.396" upper_limit="2.360"/>
                    <measurement group_id="O2" value="-7.73" lower_limit="-15.216" upper_limit="-0.245"/>
                  </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>BI 409306 vs. placebo of change from baseline at week 52, positive items score. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.5858</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-0.80</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.749</ci_lower_limit>
            <ci_upper_limit>2.153</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>BI 409306 vs. placebo of change from baseline at week 52, negative items score. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.3445</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>1.43</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.604</ci_lower_limit>
            <ci_upper_limit>4.462</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>BI 409306 vs. placebo of change from baseline at week 52, total score. Restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.7154</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Adjusted mean difference</param_type>
            <param_value>1.71</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.772</ci_lower_limit>
            <ci_upper_limit>11.196</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From treatment start date until the date of discontinuation of trial medication + 7 days, up to 381 days.</time_frame>
      <desc>The treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
        </group>
        <group group_id="E2">
          <title>BI 409306</title>
          <description>Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</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="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal behaviour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.0</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="16" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Chromatopsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyschromatopsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </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="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </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="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </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>The sponsor decided to prematurely stop enrollment. This decision was based on the unfortunate inability to meet expected enrolment goals, a situation made far worse by the impact of the COVID-19 pandemic.</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/NCT03230097
org study id: 1289.32
secondary id: 2016-004973-42
nct id: NCT03230097
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a study in people between 16 and 30 years of age who have a specific type of mental
      illness called attenuated psychosis syndrome (APS). The purpose of this study is to find out
      whether BI 409306 helps reduce the symptoms of APS.

      Participants are in the study for 1 year and 2 months. During this time, they visit the study
      site about 15 times and get about 10 phone calls. Participants are put into 2 groups by
      chance. They get either BI 409306 or placebo. Placebo tablets look like BI 409306 tablets but
      do not contain any medicine. Participants take a BI 409306 or placebo tablet two times a day.

      During the study, participants answer questions in interviews and complete questionnaires so
      the doctors can check whether the APS symptoms change. The doctors also check the general
      health of the participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe
time frame: Up to 52 weeks.
description: Incidence of remission from attenuated psychosis syndrome (APS) within a 52-week timeframe. The incidence rate per patient-years of remission from attenuated psychosis syndrome (APS) is reported. Remission from APS is defined as a score of <3 on all of the five Positive Symptom items of the Scale of Prodromal Symptoms (SOPS) and maintained until the end of treatment. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms. incidence rate = number of events/total time at risk [patient-years].
measure: Incidence of First Episode of Psychosis
time frame: Up to 52 weeks.
description: Incidence of first episode of psychosis. The incidence rate per patient-years of psychosis is reported, psychosis is defined as one or more positive Scale of Prodromal Symptoms (SOPS) symptoms rated a 6 AND either a symptom is seriously disorganizing or dangerous OR one of the symptoms above occurred at least one hour per day at an average frequency of four days/week over the past month. OR a new prescription or increase in dose of an ongoing antipsychotic medication. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms.
measure: Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment
time frame: Baseline, week 24 and week 52.
description: Change from baseline (Day -28 to -7) in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 24 and 52 weeks of treatment. 20-item assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80). Data analyzed using the restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.
measure: Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment
time frame: Baseline and week 52.
description: Change from baseline (Day -28 to -7) in the tablet based Brief Assessment of Cognition (BAC App) composite T score after 52 weeks of treatment. The BAC consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores was generated (averages five of the standardized scaled sub-test scores, token motor test score not included), larger T-score indicates better cognition. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction. T-scores in the general population have a mean of 50 and standard deviation of 10.
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment
time frame: Baseline and week 52.
description: Change from baseline (Day -28 to -7) in Positive and Negative Syndrome Scale (PANSS) positive items score, negative items score, and total score after 52 weeks of treatment. The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline NAPLS risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.
arm group label: BI 409306
arm group type: Experimental
description: Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.
intervention type: Drug
intervention name: BI 409306
description: 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.
arm group label: BI 409306
intervention type: Drug
intervention name: Placebo
description: placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 16 Years
maximum age: 30 Years
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
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country: Canada
country: China
country: United Kingdom
country: United States
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Psychotic Disorders
mesh term: BI 409306
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The sponsor decided to prematurely stop enrollment. This decision was based on the unfortunate inability to meet expected enrolment goals, a situation made far worse by the impact of the COVID-19 pandemic.
point of contact: 