<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/NCT02194933</url>
  </required_header>
  <id_info>
    <org_study_id>331-13-009</org_study_id>
    <nct_id>NCT02194933</nct_id>
  </id_info>
  <brief_title>Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Schizophrenia With Impulsivity</brief_title>
  <official_title>Protocol 331-13-009: An Exploratory, Multicenter, Randomized, Double-Blind, fMRI Study of Fixed-dose Brexpiprazole (OPC-34712) (2 and 4 mg/Day Tablets) in Adults With Schizophrenia With Impulsivity</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 evaluate the effect of brexpiprazole, via functional magnetic&#xD;
      resonance imaging (fMRI), on the right ventrolateral prefrontal cortex (VLPFC) activated by&#xD;
      impulsive behavior.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task</measure>
    <time_frame>At baseline (Day 0), and week 6 (Day 42) of the treatment phase</time_frame>
    <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) &amp; to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task</measure>
    <time_frame>At baseline (Day 0), and week 6 (Day 42) of the treatment phase</time_frame>
    <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task)</measure>
    <time_frame>At baseline (Day 0), and week 3 (Day 21) of the treatment phase</time_frame>
    <description>Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) &amp; to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes &amp; 8 seconds each. Each run included 36 target (Go) &amp; 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go &amp; 2 Neutral Go conditions.&#xD;
SSRT: White circle was shown for 500ms, followed by left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms determined participant's SSRT.&#xD;
Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)</measure>
    <time_frame>At baseline (Day 0), and Week 6 (Day 42) of the treatment.</time_frame>
    <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in BIS-11</measure>
    <time_frame>At baseline (Day 0), and Week 3 (Day 21) of the treatment.</time_frame>
    <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Go/No-go Task Behavior</measure>
    <time_frame>At baseline (Day 0), week 6 (Day 42) of the treatment phase</time_frame>
    <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in Go/No-go Task Behavior</measure>
    <time_frame>At baseline (Day 0), and week 3 (Day 21) of the treatment phase</time_frame>
    <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in MCQ Score</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior</measure>
    <time_frame>At baseline (Day 0), and Week 6 (Day 42).</time_frame>
    <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in SSRT Task Behavior</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in CPT Behavior</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in PANSS Total Score</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in PANSS Positive Subscale Score</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in PANSS Positive Subscale Score</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in PANSS Negative Subscale Score</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in PANSS Negative Subscale Score</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in CGI-S Score</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CGI-I Score at Week 3</measure>
    <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
    <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)</measure>
    <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
    <description>A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Schizophrenia With Impulsivity</condition>
  <arm_group>
    <arm_group_label>Brexpiprazole 2 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brexpiprazole 2 mg/day, once daily dose, tablet, orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Brexpiprazole 4 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brexpiprazole 4 mg/day, once daily dose, tablet, orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
    <arm_group_label>Brexpiprazole 2 mg</arm_group_label>
    <arm_group_label>Brexpiprazole 4 mg</arm_group_label>
    <other_name>OPC-34712</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Are 18 to 65 years of age, inclusive, at the time of informed consent (outpatients&#xD;
             only), with a diagnosis of schizophrenia as defined by Diagnostic and Statistical&#xD;
             Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and&#xD;
             confirmed by both the M.I.N.I. for Schizophrenia and Psychotic Disorders Studies, and&#xD;
             an adequate clinical psychiatric evaluation.&#xD;
&#xD;
          -  Have a CGI-S score of ≤ 4 (moderately ill) at screening and baseline.&#xD;
&#xD;
          -  Have a score of ≤ 4 (moderate) on PANSS item G8 (uncooperativeness) at screening and&#xD;
             baseline.&#xD;
&#xD;
          -  Have a BIS-11 score of ≥ 50 at screening and baseline.&#xD;
&#xD;
          -  Willing to discontinue all prohibited psychotropic medications to meet&#xD;
             protocol-required washouts prior to and during the trial period.&#xD;
&#xD;
          -  Are stable on their current oral antipsychotic medication (no changes within the last&#xD;
             month) and are able to meet protocol-required washouts of their current antipsychotic&#xD;
             medication.&#xD;
&#xD;
          -  Have received previous outpatient antipsychotic treatment at an adequate dose (at&#xD;
             least minimal recommended dose for the treatment of schizophrenia according to the&#xD;
             manufacturer labeling) for an adequate duration (at least 6 weeks) and showed a&#xD;
             previous good response to such antipsychotic treatment (other than clozapine) in the&#xD;
             last 12 months, according to the investigator's opinion.&#xD;
&#xD;
          -  Subjects with eyesight that is sufficient to be able to see visual displays, or&#xD;
             correctable with magnet-compatible glasses or contact lenses.&#xD;
&#xD;
          -  Subjects fluent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are presenting with schizophreniform or with a first episode of schizophrenia based on&#xD;
             the clinical judgment of the investigator.&#xD;
&#xD;
          -  Have been hospitalized for psychotic symptoms within the previous 6 months.&#xD;
&#xD;
          -  Have a current DSM-IV-TR Axis I primary diagnosis other than schizophrenia, including,&#xD;
             but not limited to, schizoaffective disorder, major depressive disorder, bipolar&#xD;
             disorder, post-traumatic stress disorder, obsessive-compulsive disorder (OCD) or panic&#xD;
             disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, subjects&#xD;
             with borderline, paranoid, histrionic, schizotypal, schizoid, antisocial personality&#xD;
             disorders, or mental retardation.&#xD;
&#xD;
          -  Have worsening of ≥ 20% in total PANSS score between the screening and baseline&#xD;
             assessments.&#xD;
&#xD;
          -  Experiencing a deterioration in clinical status or an acute exacerbation of&#xD;
             schizophrenia in the opinion of the Investigator.&#xD;
&#xD;
          -  Experiencing acute onset of clinically significant depressive symptoms within the past&#xD;
             30 days, according to the investigator's opinion.&#xD;
&#xD;
          -  Answer &quot;Yes&quot; on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation&#xD;
             Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and&#xD;
             whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the&#xD;
             last 6 months, OR Answer &quot;Yes&quot; on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal&#xD;
             Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria&#xD;
             for this C-SSRS Item 5 occurred within the last 6 months OR Answer &quot;Yes&quot; on any of the&#xD;
             5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted&#xD;
             attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria&#xD;
             for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR&#xD;
             who, in the opinion of the investigator, present a serious risk of suicide.&#xD;
&#xD;
          -  Have a history of stroke.&#xD;
&#xD;
          -  Contraindications to magnetic resonance imaging (MRI) such as metal prostheses,&#xD;
             pacemakers, claustrophobia, movement disorders, waist circumference more than 56&#xD;
             inches or head circumference more than 29 inches, color blindness, significant&#xD;
             tremors, or history of head injury or prolonged unconsciousness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California at Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>May 3, 2017</results_first_submitted>
  <results_first_submitted_qc>August 10, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 11, 2018</results_first_posted>
  <last_update_submitted>October 9, 2018</last_update_submitted>
  <last_update_submitted_qc>October 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Mental Disorders, Antipsychotic,</keyword>
  <keyword>Psychotic disorder, Impulsivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Impulsive Behavior</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brexpiprazole</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted in the United States (US). 38 participants with schizophrenia with impulsivity were enrolled (signed informed consent) and randomized (1:1): 19 participants to brexpiprazole 2mg and 4mg treatment each; received at least 1 dose of Investigational medicinal product (IMP) for 6-week treatment phase in a double-blind design.</recruitment_details>
      <pre_assignment_details>Participants had pretreatment screening phase from 2 to 21 days to assess eligibility criteria, complete screening assessments &amp; to wash out from prior antipsychotic drugs &amp; any other prohibited concomitant drugs; participants were followed for safety by clinic visits/telephone (after first 3 to 4 days of antipsychotic washout &amp; weekly as needed).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Brexpiprazole 2 mg</title>
          <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
        </group>
        <group group_id="P2">
          <title>Brexpiprazole 4 mg</title>
          <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant met withdrawal criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Brexpiprazole 2 mg</title>
          <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
        </group>
        <group group_id="B2">
          <title>Brexpiprazole 4 mg</title>
          <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</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="19"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>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="45.2" spread="10.0"/>
                    <measurement group_id="B2" value="47.4" spread="11.1"/>
                    <measurement group_id="B3" value="46.3" spread="10.5"/>
                  </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="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race</title>
          <description>Different races were involved in this study</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Caucasian (White)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African or American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Others</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethinicity</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hispanic/Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic/Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task</title>
        <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) &amp; to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
        <time_frame>At baseline (Day 0), and week 6 (Day 42) of the treatment phase</time_frame>
        <population>All participants who had a valid baseline and a Week 6 fMRI scan assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task</title>
          <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) &amp; to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
          <population>All participants who had a valid baseline and a Week 6 fMRI scan assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06450" spread="0.02815"/>
                    <measurement group_id="O2" value="0.06609" spread="0.02875"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04949" spread="0.02878"/>
                    <measurement group_id="O2" value="0.04326" spread="0.03128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3992</p_value>
            <p_value_desc>Test for Baseline vs. Week 6</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task</title>
        <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
        <time_frame>At baseline (Day 0), and week 6 (Day 42) of the treatment phase</time_frame>
        <population>All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task</title>
          <description>To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
          <population>All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05200" spread="0.02993"/>
                    <measurement group_id="O2" value="0.09485" spread="0.03428"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.00140" spread="0.03048"/>
                    <measurement group_id="O2" value="0.002815" spread="0.03541"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0053</p_value>
            <p_value_desc>Test for Baseline vs. Week 6</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task)</title>
        <description>Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) &amp; to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes &amp; 8 seconds each. Each run included 36 target (Go) &amp; 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go &amp; 2 Neutral Go conditions.&#xD;
SSRT: White circle was shown for 500ms, followed by left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms determined participant's SSRT.&#xD;
Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
        <time_frame>At baseline (Day 0), and week 3 (Day 21) of the treatment phase</time_frame>
        <population>All participants who had a valid baseline and a valid Week 3 fMRI scan assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task)</title>
          <description>Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) &amp; to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes &amp; 8 seconds each. Each run included 36 target (Go) &amp; 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go &amp; 2 Neutral Go conditions.&#xD;
SSRT: White circle was shown for 500ms, followed by left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms determined participant's SSRT.&#xD;
Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.</description>
          <population>All participants who had a valid baseline and a valid Week 3 fMRI scan assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>GNG; Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06347" spread="0.02801"/>
                    <measurement group_id="O2" value="0.06553" spread="0.02869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GNG; Week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08523" spread="0.02801"/>
                    <measurement group_id="O2" value="0.04973" spread="0.02869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SSRT; Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05376" spread="0.02903"/>
                    <measurement group_id="O2" value="0.09550" spread="0.03346"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SSRT; Week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06398" spread="0.02979"/>
                    <measurement group_id="O2" value="0.02410" spread="0.03346"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)</title>
        <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
        <time_frame>At baseline (Day 0), and Week 6 (Day 42) of the treatment.</time_frame>
        <population>The full analysis set consisted of all participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. Change from baseline data were presented for participant count of 16, 12 for 2mg and 4mg arms, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)</title>
          <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
          <population>The full analysis set consisted of all participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. Change from baseline data were presented for participant count of 16, 12 for 2mg and 4mg arms, respectively.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" spread="1.8"/>
                    <measurement group_id="O2" value="1.0" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1559</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6201</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in BIS-11</title>
        <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
        <time_frame>At baseline (Day 0), and Week 3 (Day 21) of the treatment.</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in BIS-11</title>
          <description>A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="1.7"/>
                    <measurement group_id="O2" value="-2.3" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1642</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1873</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Go/No-go Task Behavior</title>
        <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
        <time_frame>At baseline (Day 0), week 6 (Day 42) of the treatment phase</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Go/No-go Task Behavior</title>
          <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>Millisecond</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="0.08"/>
                    <measurement group_id="O2" value="0.09" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" spread="0.09"/>
                    <measurement group_id="O2" value="0.12" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in Go/No-go Task Behavior</title>
        <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
        <time_frame>At baseline (Day 0), and week 3 (Day 21) of the treatment phase</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in Go/No-go Task Behavior</title>
          <description>Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>Millisecond</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="0.08"/>
                    <measurement group_id="O2" value="0.09" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" spread="0.13"/>
                    <measurement group_id="O2" value="0.15" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score</title>
        <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score</title>
          <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.019762" spread="0.015213"/>
                    <measurement group_id="O2" value="0.023685" spread="0.017103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2061</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1778</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in MCQ Score</title>
        <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in MCQ Score</title>
          <description>To measure &quot;delay discounting&quot; as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?&quot;). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.012073" spread="0.014558"/>
                    <measurement group_id="O2" value="0.014520" spread="0.014891"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4138</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3375</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior</title>
        <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
        <time_frame>At baseline (Day 0), and Week 6 (Day 42).</time_frame>
        <population>All participants who had a valid baseline and a valid Week 6 fMRI scan assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior</title>
          <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
          <population>All participants who had a valid baseline and a valid Week 6 fMRI scan assessment</population>
          <units>Millisecond</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="357.63" spread="61.51"/>
                    <measurement group_id="O2" value="323.25" spread="56.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="299.68" spread="67.77"/>
                    <measurement group_id="O2" value="302.57" spread="34.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in SSRT Task Behavior</title>
        <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who had a valid baseline and a valid Week 3 fMRI scan assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in SSRT Task Behavior</title>
          <description>Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (&lt;)/right (&gt;) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 &amp; 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes &amp; 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with &amp; without a response</description>
          <population>All participants who had a valid baseline and a valid Week 3 fMRI scan assessment</population>
          <units>Millisecond</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="357.63" spread="61.51"/>
                    <measurement group_id="O2" value="323.25" spread="56.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="337.62" spread="76.23"/>
                    <measurement group_id="O2" value="328.05" spread="54.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior</title>
        <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Brexpiprazole 2 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Brexpiprazole 4 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior</title>
          <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
          <units>Rate of correct response</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.70" spread="3.50"/>
                    <measurement group_id="O2" value="-0.87" spread="4.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8437</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8318</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in CPT Behavior</title>
        <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in CPT Behavior</title>
          <description>The AX trials were &quot;target trials&quot; with a valid cue followed by a valid probe X. This feature was intended to encourage participants to &quot;expect&quot; a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with &quot;target&quot; responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the &quot;Yes&quot; button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>Rate of correct response</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.79" spread="4.14"/>
                    <measurement group_id="O2" value="-0.61" spread="4.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6697</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8829</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score</title>
        <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score</title>
          <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="1.9"/>
                    <measurement group_id="O2" value="-4.1" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2301</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0599</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in PANSS Total Score</title>
        <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in PANSS Total Score</title>
          <description>The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="1.4"/>
                    <measurement group_id="O2" value="-2.3" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1595</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1211</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in PANSS Positive Subscale Score</title>
        <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in PANSS Positive Subscale Score</title>
          <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="0.9"/>
                    <measurement group_id="O2" value="-1.3" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1322</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2113</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in PANSS Positive Subscale Score</title>
        <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in PANSS Positive Subscale Score</title>
          <description>PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="0.6"/>
                    <measurement group_id="O2" value="-1.3" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0578</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0588</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in PANSS Negative Subscale Score</title>
        <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in PANSS Negative Subscale Score</title>
          <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="0.6"/>
                    <measurement group_id="O2" value="0.2" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1666</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.7670</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in PANSS Negative Subscale Score</title>
        <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in PANSS Negative Subscale Score</title>
          <description>PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.7"/>
                    <measurement group_id="O2" value="0.8" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.7178</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2336</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score</title>
        <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score</title>
          <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.1"/>
                    <measurement group_id="O2" value="0.0" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6558</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9058</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in CGI-S Score</title>
        <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in CGI-S Score</title>
          <description>The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="0.1"/>
                    <measurement group_id="O2" value="-0.1" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0078</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4272</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6</title>
        <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6</title>
          <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="1.0"/>
                    <measurement group_id="O2" value="3.9" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CGI-I Score at Week 3</title>
        <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
        <time_frame>During trial visits from Day 0 to Week 3 (Day 21).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.</description>
          </group>
        </group_list>
        <measure>
          <title>CGI-I Score at Week 3</title>
          <description>To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="0.8"/>
                    <measurement group_id="O2" value="3.8" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)</title>
        <description>A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.</description>
        <time_frame>During trial visits from Day 0 to Week 6 (Day 42).</time_frame>
        <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole 2 mg</title>
            <description>Brexpiprazole 2 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole 4 mg</title>
            <description>Brexpiprazole 4 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)</title>
          <description>A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.</description>
          <population>All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="1.6"/>
                    <measurement group_id="O2" value="-0.0" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Trial visits (Days 0 to 42)</time_frame>
      <desc>An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, &quot;reasonable possibility&quot; meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention</desc>
      <group_list>
        <group group_id="E1">
          <title>Brexpiprazole 2 mg</title>
          <description>Brexpiprazole 2 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
        </group>
        <group group_id="E2">
          <title>Brexpiprazole 4 mg</title>
          <description>Brexpiprazole 4 mg/day, once daily dose, tablet, orally&#xD;
Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <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="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Preferred Ter</default_vocab>
        <default_assessment>Non-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="13" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </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="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Extrapyramidal disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </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="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Hyperkeratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Clinical Development</name_or_title>
      <organization>Otsuka Data Transparency Organization</organization>
      <email>DT-inquiry@otsuka.jp</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/NCT02194933
org study id: 331-13-009
nct id: NCT02194933
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the effect of brexpiprazole, via functional magnetic
      resonance imaging (fMRI), on the right ventrolateral prefrontal cortex (VLPFC) activated by
      impulsive behavior.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task
time frame: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
description: To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) & to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
measure: Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task
time frame: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
description: To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
measure: Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task)
time frame: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
description: Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) & to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes & 8 seconds each. Each run included 36 target (Go) & 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go & 2 Neutral Go conditions.
SSRT: White circle was shown for 500ms, followed by left (<)/right (>) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 & 250ms determined participant's SSRT.
Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
measure: Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)
time frame: At baseline (Day 0), and Week 6 (Day 42) of the treatment.
description: A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.
measure: Change From Baseline to Week 3 in BIS-11
time frame: At baseline (Day 0), and Week 3 (Day 21) of the treatment.
description: A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.
measure: Change From Baseline to Week 6 in Go/No-go Task Behavior
time frame: At baseline (Day 0), week 6 (Day 42) of the treatment phase
description: Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).
measure: Change From Baseline to Week 3 in Go/No-go Task Behavior
time frame: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
description: Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).
measure: Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ
measure: Change From Baseline to Week 3 in MCQ Score
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.
measure: Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior
time frame: At baseline (Day 0), and Week 6 (Day 42).
description: Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response
measure: Change From Baseline to Week 3 in SSRT Task Behavior
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response
measure: Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.
measure: Change From Baseline to Week 3 in CPT Behavior
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.
measure: Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.
measure: Change From Baseline to Week 3 in PANSS Total Score
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.
measure: Change From Baseline to Week 6 in PANSS Positive Subscale Score
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
measure: Change From Baseline to Week 3 in PANSS Positive Subscale Score
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
measure: Change From Baseline to Week 6 in PANSS Negative Subscale Score
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
measure: Change From Baseline to Week 3 in PANSS Negative Subscale Score
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
measure: Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
measure: Change From Baseline to Week 3 in CGI-S Score
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
measure: Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).
measure: CGI-I Score at Week 3
time frame: During trial visits from Day 0 to Week 3 (Day 21).
description: To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).
measure: Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)
time frame: During trial visits from Day 0 to Week 6 (Day 42).
description: A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.
arm group label: Brexpiprazole 2 mg
arm group type: Experimental
description: Brexpiprazole 2 mg/day, once daily dose, tablet, orally
arm group label: Brexpiprazole 4 mg
arm group type: Experimental
description: Brexpiprazole 4 mg/day, once daily dose, tablet, orally
intervention type: Drug
intervention name: Brexpiprazole
description: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks
arm group label: Brexpiprazole 2 mg
arm group label: Brexpiprazole 4 mg
other name: OPC-34712
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Impulsive Behavior
mesh term: Brexpiprazole
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 