<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/NCT03238326</url>
  </required_header>
  <id_info>
    <org_study_id>331-10-236</org_study_id>
    <nct_id>NCT03238326</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of Open-Label Flexible-dose Brexpiprazole as Maintenance Treatment in Adolescents With Schizophrenia</brief_title>
  <official_title>A Long-term, Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Flexible-Dose Brexpiprazole as Maintenance Treatment in Adolescents (13-17 Years Old) With Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>H. Lundbeck A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</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>
      To further characterize the long-term safety and tolerability of brexpiprazole in adolescents&#xD;
      with schizophrenia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a long-term, multicenter, open-label trial designed to examine the long-term safety&#xD;
      and tolerability of brexpiprazole in adolescent subjects (ages 13-17) with a DSM-5 diagnosis&#xD;
      of schizophrenia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 23, 2017</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency &amp; Severity of Adverse Events (AE) [Safety]</measure>
    <time_frame>Up to 24 months or early termination with a 21 day follow-up period</time_frame>
    <description>Frequency and severity will be monitored; along with serious AEs &amp; discontinuation from trial due to AE</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline and incidence of clinically significant abnormalities in clinical laboratory tests [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Abnormalities in hematology, serum chemistry [including fasting blood lipids, glucose and insulin, serum prolactin], glycosylated hemoglobin [HbA1c], creatine phosphokinase [CPK] and urinalysis) results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline and incidence of clinically significant abnormalities in vital signs [Safety]</measure>
    <time_frame>Up to 24 months or early termination with a 21 day follow-up period</time_frame>
    <description>Mean change from baseline in supine and standing positions will be assessed and incidence of clinically significant abnormalities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Change in weight, in kilograms, will be assessed for any notable differences from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Change in height, in centimeters, will be assessed for any notable differences from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index (BMI) [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Measured in kilograms/meter^2 and assessed to determine any notable differences from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist Circumference [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Change in waist circumference, in centimeters will be assessed for any notable differences from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ECG [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Mean change from baseline will be assessed and incidence of clinically significant abnormalities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Abnormal Involuntary Movement Scale (AIMS) Score [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Mean change from baseline will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Simpson-Angus Scale (SAS) Score [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Mean change from baseline will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Barnes Akathisia Rating Scale (BARS) Score [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Mean change from baseline will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential suicide events recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS) [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Analysis of potential suicide events recorded with C SSRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comprehensive psychotropic side effects as assessed by Udvalg for Kliniske Undersogelser (UKU) [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Psychotropic side effects will be assessed by UKU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The frequency of symptom items from New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Frequency of symptom items will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tanner Staging Scale Scores [Safety]</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Baseline and post-baseline data will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to discontinuation due to AE</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Time to discontinue will be assessed as applicable</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Positive and Negative Syndrome Scale (PANSS) Total Score and PANSS Subscale Scores</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Change from baseline in total score will be assessed for efficacy of drug. Positive/Negative subscale scores will be assessed for efficacy of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Children's Global Assessment Scale (CGAS) Score</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
    <description>Change from baseline in CGAS will be assessed for efficacy of drug</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impression Severity (CGI-S) Score</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impression Improvement (CGI-I) Score</measure>
    <time_frame>Up to 24 months or early termination</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">296</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Rollover &amp; De-Novo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1-4 mg/day; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Once daily, oral tablets</description>
    <arm_group_label>Rollover &amp; De-Novo</arm_group_label>
    <other_name>OPC-34712</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male &amp; female subjects 13-17 years of age, inclusive.&#xD;
&#xD;
          -  Subjects who turn 18 during trial 331-10-234 are permitted in this trial.&#xD;
&#xD;
          -  Subjects with a current primary diagnosis of schizophrenia, as defined by Diagnostic&#xD;
             and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria and confirmed&#xD;
             by the K-SADS-PL completed at time of entry into Trial 331-10-234. For de novo&#xD;
             subjects who did not participate in Trial 331-10-234, the initial diagnosis of&#xD;
             schizophrenia must be made and documented, and the diagnosis confirmed by the&#xD;
             K-SADS-PL at screening.&#xD;
&#xD;
          -  Subjects who, in the investigator's judgment, require treatment with antipsychotic&#xD;
             medication(s).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a DSM-5 diagnosis other than schizophrenia that has been the primary&#xD;
             focus of treatment within 3 months of screening&#xD;
&#xD;
          -  Subjects with a clinical presentation or history that is consistent with delirium,&#xD;
             dementia, amnesia, or other cognitive disorders; subjects with psychotic symptoms that&#xD;
             are better accounted for by another general medical condition(s) or direct effect of a&#xD;
             substance (e.g., medication, illicit drug use).&#xD;
&#xD;
          -  History of failure of clozapine treatment or response to clozapine treatment only.&#xD;
&#xD;
          -  History of neuroleptic malignant syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuko Hirata, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>For additional information regarding sites, contact 844-687-8522</name>
      <address>
        <city>Kinston</city>
        <state>North Carolina</state>
        <zip>28501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Serbia</country>
    <country>Ukraine</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>August 2, 2023</last_update_submitted>
  <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brexpiprazole</keyword>
  <keyword>Schizophrenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brexpiprazole</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03238326
org study id: 331-10-236
nct id: NCT03238326
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To further characterize the long-term safety and tolerability of brexpiprazole in adolescents
      with schizophrenia
This is a long-term, multicenter, open-label trial designed to examine the long-term safety
      and tolerability of brexpiprazole in adolescent subjects (ages 13-17) with a DSM-5 diagnosis
      of schizophrenia.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Frequency & Severity of Adverse Events (AE) [Safety]
time frame: Up to 24 months or early termination with a 21 day follow-up period
description: Frequency and severity will be monitored; along with serious AEs & discontinuation from trial due to AE
measure: Mean change from baseline and incidence of clinically significant abnormalities in clinical laboratory tests [Safety]
time frame: Up to 24 months or early termination
description: Abnormalities in hematology, serum chemistry [including fasting blood lipids, glucose and insulin, serum prolactin], glycosylated hemoglobin [HbA1c], creatine phosphokinase [CPK] and urinalysis) results
measure: Mean change from baseline and incidence of clinically significant abnormalities in vital signs [Safety]
time frame: Up to 24 months or early termination with a 21 day follow-up period
description: Mean change from baseline in supine and standing positions will be assessed and incidence of clinically significant abnormalities
measure: Weight [Safety]
time frame: Up to 24 months or early termination
description: Change in weight, in kilograms, will be assessed for any notable differences from baseline
measure: Height [Safety]
time frame: Up to 24 months or early termination
description: Change in height, in centimeters, will be assessed for any notable differences from baseline
measure: Body Mass Index (BMI) [Safety]
time frame: Up to 24 months or early termination
description: Measured in kilograms/meter^2 and assessed to determine any notable differences from baseline
measure: Waist Circumference [Safety]
time frame: Up to 24 months or early termination
description: Change in waist circumference, in centimeters will be assessed for any notable differences from baseline
measure: Changes in ECG [Safety]
time frame: Up to 24 months or early termination
description: Mean change from baseline will be assessed and incidence of clinically significant abnormalities
measure: Change in Abnormal Involuntary Movement Scale (AIMS) Score [Safety]
time frame: Up to 24 months or early termination
description: Mean change from baseline will be assessed
measure: Change in Simpson-Angus Scale (SAS) Score [Safety]
time frame: Up to 24 months or early termination
description: Mean change from baseline will be assessed
measure: Change in Barnes Akathisia Rating Scale (BARS) Score [Safety]
time frame: Up to 24 months or early termination
description: Mean change from baseline will be assessed
measure: Potential suicide events recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS) [Safety]
time frame: Up to 24 months or early termination
description: Analysis of potential suicide events recorded with C SSRS
measure: Comprehensive psychotropic side effects as assessed by Udvalg for Kliniske Undersogelser (UKU) [Safety]
time frame: Up to 24 months or early termination
description: Psychotropic side effects will be assessed by UKU
measure: The frequency of symptom items from New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) [Safety]
time frame: Up to 24 months or early termination
description: Frequency of symptom items will be assessed
measure: Change in Tanner Staging Scale Scores [Safety]
time frame: Up to 24 months or early termination
description: Baseline and post-baseline data will be assessed
measure: Time to discontinuation due to AE
time frame: Up to 24 months or early termination
description: Time to discontinue will be assessed as applicable
measure: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score and PANSS Subscale Scores
time frame: Up to 24 months or early termination
description: Change from baseline in total score will be assessed for efficacy of drug. Positive/Negative subscale scores will be assessed for efficacy of drug.
measure: Change in Children's Global Assessment Scale (CGAS) Score
time frame: Up to 24 months or early termination
description: Change from baseline in CGAS will be assessed for efficacy of drug
measure: Change in Clinical Global Impression Severity (CGI-S) Score
time frame: Up to 24 months or early termination
measure: Change in Clinical Global Impression Improvement (CGI-I) Score
time frame: Up to 24 months or early termination
arm group label: Rollover & De-Novo
arm group type: Experimental
description: 1-4 mg/day; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day
intervention type: Drug
intervention name: Brexpiprazole
description: Once daily, oral tablets
arm group label: Rollover & De-Novo
other name: OPC-34712
criteria: 
gender: All
minimum age: 13 Years
maximum age: 17 Years
healthy volunteers: No
last name: Yuko Hirata, MD, PhD
role: Study Director
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
facility: 
country: United States
country: Serbia
country: Ukraine
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Brexpiprazole