<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/NCT02212613</url>
  </required_header>
  <id_info>
    <org_study_id>331-13-004</org_study_id>
    <nct_id>NCT02212613</nct_id>
  </id_info>
  <brief_title>Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability</brief_title>
  <official_title>Protocol 331-13-004: An Exploratory, Multicenter, Single-blind, fMRI Study of Fixed-dose Brexpiprazole (OPC 34712) (2 mg/Day Tablets) as an Adjunctive Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the effects of fixed-dosed brexpiprazole adjunctive&#xD;
      treatment in subjects with Major Depressive Disorder with irritability&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Low enrollment&#xD;
  </why_stopped>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in functional magnetic resonance imaging (fMRI) BOLD activation score in the ventromedial prefrontal cortex and amygdala, scanned by fMRI during performance of the Emotion-induction Task</measure>
    <time_frame>Week 6</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Spielberger State Trait Anger Expression Inventory (STAXI-2) Part 1</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Visual Analog Scale (VAS)</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) score</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Improvement Scale (CGI-I) score at Phase B Week 6</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Phase B baseline to Phase B Week 6</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Phase B baseline to Phase B Week 6</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Sheehan Disability Scale (SDS) 3-item mean score</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Anger Attacks Questionnaire (AAQ) score</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Symptoms of Depression Questionnaire (SDQ)</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Kellner Symptom Questionnaire (KSQ)</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Phase B baseline to Phase B Week 6 in Barratt Impulsiveness Scale 11 item (BIS-11) Total Score</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Major Depressive Disorder and Irritability</condition>
  <arm_group>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brexpiprazole - Up to 2 mg/day, once daily dose, tablets, orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Treatment (6 weeks) Up to 2 mg/day, once daily dose, tablets, orally</description>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <other_name>OPC-34712</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Inclusion Criteria:&#xD;
&#xD;
               -  Are 18 to 55 years of age, inclusive, at the time of informed consent with a&#xD;
                  diagnosis of a single or recurrent, nonpsychotic episode of MDD as defined by the&#xD;
                  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text&#xD;
                  Revision (DSM-IV-TR™) and confirmed by the Mini International Neuropsychiatric&#xD;
                  Interview (M.I.N.I.) and an adequate clinical psychiatric evaluation&#xD;
&#xD;
               -  Have received a single, trial-approved SSRI or SNRI at an adequate dose for ≥ 6&#xD;
                  weeks prior to screening&#xD;
&#xD;
               -  Have a treatment history of inadequate ADT response to at least one ADT (but not&#xD;
                  &gt; 3) for the current episode. The current major depressive episode must be ≥ 6&#xD;
                  weeks in duration. (An inadequate ADT response is defined as &lt; 50% reduction in&#xD;
                  depressive symptom severity, as measured by subject self-report on the MGH-ATRQ.)&#xD;
&#xD;
               -  To be eligible for this trial&#xD;
&#xD;
                    -  Have a MADRS Total Score of 20 or more at screening and the Phase A&#xD;
                       baseline, and have a MADRS Total Score of 18 or more at the Phase B baseline&#xD;
&#xD;
                    -  Have no more than 20% improvement in MADRS Total Score at Phase B baseline&#xD;
                       compared to Phase A baseline&#xD;
&#xD;
                    -  Have a score of 6 or more on the KSQ based on the Well being and Reversal&#xD;
                       Distress Anger-hostility subscales at screening, Phase A baseline, and Phase&#xD;
                       B baseline&#xD;
&#xD;
                    -  Have anger attacks as documented by the AAQ at screening, Phase A baseline,&#xD;
                       and Phase B baseline&#xD;
&#xD;
               -  Are right-handed (defined according to the Edinburgh Handedness Inventory) and&#xD;
                  have normal hearing and normal/corrected-to-normal vision&#xD;
&#xD;
               -  Are willing to discontinue all prohibited psychotropic medications to meet&#xD;
                  protocol-required washouts prior to and during the trial period&#xD;
&#xD;
               -  Eligibility confirmed through a telephone SAFER interview with the subject and an&#xD;
                  independent expert centralized rater&#xD;
&#xD;
          -  Exclusion Criteria:&#xD;
&#xD;
               -  Have a current need for involuntary commitment or have been hospitalized within 4&#xD;
                  weeks of screening for the current major depressive episode&#xD;
&#xD;
               -  Have a current DSM-IV-TR Axis I diagnosis of any of the following: delirium,&#xD;
                  dementia, amnestic, or other cognitive disorders; schizophrenia, schizoaffective&#xD;
                  disorder, or other psychotic disorders; bipolar I disorder, bipolar II disorder,&#xD;
                  or bipolar disorder not otherwise specified; eating disorders (including anorexia&#xD;
                  nervosa or bulimia); obsessive compulsive disorder; panic disorder; or&#xD;
                  post-traumatic stress disorder&#xD;
&#xD;
               -  Have any of the following current Axis II DSM-IV-TR diagnoses: borderline,&#xD;
                  antisocial, paranoid, schizoid, schizotypal or histrionic personality disorders,&#xD;
                  or mental retardation&#xD;
&#xD;
               -  Experiencing hallucinations, delusions, or any psychotic symptomatology in the&#xD;
                  current major depressive episode&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Junichi Hashimoto, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>July 5, 2016</last_update_submitted>
  <last_update_submitted_qc>July 5, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 7, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Mental Disorders, nonpsychotic episode, antipsychotic</keyword>
  <keyword>Mood Disorder, psychotic disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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/NCT02212613
org study id: 331-13-004
nct id: NCT02212613
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to explore the effects of fixed-dosed brexpiprazole adjunctive
      treatment in subjects with Major Depressive Disorder with irritability
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Change from Phase B baseline to Phase B Week 6 in functional magnetic resonance imaging (fMRI) BOLD activation score in the ventromedial prefrontal cortex and amygdala, scanned by fMRI during performance of the Emotion-induction Task
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Spielberger State Trait Anger Expression Inventory (STAXI-2) Part 1
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Visual Analog Scale (VAS)
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) score
time frame: Week 6
measure: Clinical Global Impression - Improvement Scale (CGI-I) score at Phase B Week 6
time frame: Week 6
measure: MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Phase B baseline to Phase B Week 6
time frame: Week 6
measure: MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Phase B baseline to Phase B Week 6
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Sheehan Disability Scale (SDS) 3-item mean score
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Anger Attacks Questionnaire (AAQ) score
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Symptoms of Depression Questionnaire (SDQ)
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Kellner Symptom Questionnaire (KSQ)
time frame: Week 6
measure: Change from Phase B baseline to Phase B Week 6 in Barratt Impulsiveness Scale 11 item (BIS-11) Total Score
time frame: Week 6
arm group label: Brexpiprazole
arm group type: Experimental
description: Brexpiprazole - Up to 2 mg/day, once daily dose, tablets, orally
intervention type: Drug
intervention name: Brexpiprazole
description: Treatment (6 weeks) Up to 2 mg/day, once daily dose, tablets, orally
arm group label: Brexpiprazole
other name: OPC-34712
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Junichi Hashimoto, PhD
role: Study Director
affiliation: Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Brexpiprazole