<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/NCT03287869</url>
  </required_header>
  <id_info>
    <org_study_id>331-201-00083</org_study_id>
    <secondary_id>2017-002225-38</secondary_id>
    <nct_id>NCT03287869</nct_id>
  </id_info>
  <brief_title>A Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Participants With Bipolar I Disorder.</brief_title>
  <official_title>A Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Subjects With Bipolar I Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>H. Lundbeck A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluated the safety and evaluate the safety and tolerability of open-label&#xD;
      brexpiprazole (2 - 4 mg/day, with a starting dose of 2 mg/day) for the treatment of adult&#xD;
      subjects with bipolar I disorder. All participants received a starting dose of brexpiprazole.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While the availability of atypical antipsychotics had increased the therapeutic options&#xD;
      available, there remains a need for safer and more effective therapies in the treatment of&#xD;
      manic and depressive episodes of bipolar I disorder. Brexpiprazole's specific receptor&#xD;
      activity profile likely correlates with its established efficacy in schizophrenia and major&#xD;
      depressive disorder, and may prove to be an effective target for the treatment of acute mania&#xD;
      of bipolar I disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Group composed of eligible rollover participants who completed one of the double-blind, phase 3 efficacy trials (331-201-00080 (NCT03259555) or 331-201-00081 (NCT03257865)).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity</measure>
    <time_frame>From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)</time_frame>
    <description>An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">381</enrollment>
  <condition>Bipolar I Disorder</condition>
  <condition>Acute Mania</condition>
  <arm_group>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Brexpiprazole tablets</description>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <other_name>OPC-34712</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (rollover participants from 331-201-00080 &amp; 331-201-00081 trials)&#xD;
&#xD;
          -  Participants remaining in hospital at the Day 21 visit of trial 331-201-00080 or&#xD;
             331-201-00081 were permitted to enroll in the 331-201-00083 trial at the week 3 visit&#xD;
             of the double-blind trial if they were planned to be discharged from the hospital&#xD;
             before the week 1 visit of trial 331-201-0083. Participants not discharged by the week&#xD;
             1 visit of trial 331-201-0083 were withdrawn.&#xD;
&#xD;
          -  Participants who, in the opinion of the investigator, could potentially benefit from&#xD;
             administration of oral brexpiprazole for the treatment of bipolar I disorder and who&#xD;
             completed 3 weeks of post-randomization treatment in Trial 331-201-00080 &amp; Trial&#xD;
             331-201-00081.&#xD;
&#xD;
        Exclusion Criteria (rollover participants from 331-201-00080 &amp; 331-201-00081 trials)&#xD;
&#xD;
          -  Participants with a major protocol violation during the course of their participation&#xD;
             in the double-blind phase 3 trials (331-201-00080 or 331-201-00081).&#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>Woodland International Research Group</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Woodland Research Northwest, LLC</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Citrials Inc.</name>
      <address>
        <city>Bellflower</city>
        <state>California</state>
        <zip>90706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Cerritos</city>
        <state>California</state>
        <zip>90703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProScience Research Group</name>
      <address>
        <city>Culver City</city>
        <state>California</state>
        <zip>90230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Behavioral Research Specialists, LLC</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Apostle Clinical Trials</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Partners, LLC</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NRC Research Institute</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asclepes Research Centers, PC</name>
      <address>
        <city>Panorama City</city>
        <state>California</state>
        <zip>91402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Trials</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNRI-San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Artemis Institute for Clinical Research</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Mesa Vista Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Trials</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shreenath Clinical Service</name>
      <address>
        <city>Yorba Linda</city>
        <state>California</state>
        <zip>92886</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Optimus U Corp</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Segal Trials</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galiz Research</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Centers of America, LLC</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Behavioral Medicine</name>
      <address>
        <city>Largo</city>
        <state>Florida</state>
        <zip>33770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida Board of Trustees</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>iResearch Atlanta, LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Center for Psychiatric Research</name>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NeuroPsychiatric Research</name>
      <address>
        <city>Winfield</city>
        <state>Illinois</state>
        <zip>60190</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Clinical Research</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CBH Health</name>
      <address>
        <city>Gaithersburg</city>
        <state>Maryland</state>
        <zip>20877</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Charles Psychiatric Associates</name>
      <address>
        <city>Saint Charles</city>
        <state>Missouri</state>
        <zip>63304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arch Clinical Trials, LLC</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Clinical Trials</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hassman Research Institute, LLC</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of America-NC, LLC</name>
      <address>
        <city>Hickory</city>
        <state>North Carolina</state>
        <zip>28601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richard H Weisler, MD PA Associates</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SP Research PLLC</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cutting Edge Research Group</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Clinical Research, Inc.</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78754</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>InSite Clinical Research</name>
      <address>
        <city>DeSoto</city>
        <state>Texas</state>
        <zip>75115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Texas Clinical Trials</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pillar Clinical Research LLC</name>
      <address>
        <city>Garland</city>
        <state>Texas</state>
        <zip>75042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pillar Clinical Research, LLC</name>
      <address>
        <city>Richardson</city>
        <state>Texas</state>
        <zip>75080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Core Clinical Research</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Columbia Research</name>
      <address>
        <city>Richland</city>
        <state>Washington</state>
        <zip>99352</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD, Department for Treatment of Emergency Psychiatric Condition</name>
      <address>
        <city>Burgas</city>
        <zip>8000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatry Hospital - Kardzhali,Third Male Department, First Female Department</name>
      <address>
        <city>Kardzhali</city>
        <zip>6600</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatry Hospital Sv. Ivan Rilski, First Male department, First Female Department</name>
      <address>
        <city>Novi Iskar</city>
        <zip>1282</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital for Active Treatment Sveti Georgi EAD, Clinic of Psychiatry</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Mental Health Centre-Ruse&quot; EOOD, Male department for persons with severe mental disorders, Female department for persons with severe mental disorders</name>
      <address>
        <city>Ruse</city>
        <zip>7003</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital for Active Treatment -Alexandrovska EAD, Clinic of Psychiatry, First Department of Psychiatry</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment - Targovishte AD, Department of Psychiatry</name>
      <address>
        <city>Targovishte</city>
        <zip>7700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center - Veliko Tarnovo EOOD, Department of Psychiatry for Active Treatment of Persons with Severe Mental Disorders</name>
      <address>
        <city>Veliko Tarnovo</city>
        <zip>5000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center - Vratsa EOOD, Department of Psychiatry</name>
      <address>
        <city>Vratsa</city>
        <zip>3000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHC Rijeka-Clinic for Psychiatrics</name>
      <address>
        <city>Rijeka</city>
        <zip>51000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poliklinika Neuron /Polyclinic Neuron</name>
      <address>
        <city>Zagreb</city>
        <zip>10000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indywidualna Specjalistyczna Praktyka Lekarska Wieslaw Jerzy Cubala</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-438</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Prywatna Klinika Psychiatryczna Inventiva</name>
      <address>
        <city>Tuszyn</city>
        <zip>95-080</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHC Dr Dragisa Misovic</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic for Psychiatric Disorders, Dr Laza Lazarevic</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic for Psychiatry</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialized Hospital for Psychiatry Diseases Kovin</name>
      <address>
        <city>Kovin</city>
        <zip>26220</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Kragujevac, Clinic of Psychiatry</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika za psihijariju, Klinicki Centar Vojvodine</name>
      <address>
        <city>Novi Sad</city>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Clinical Hospital n.a I.I. Mechnicov</name>
      <address>
        <city>Dnipro</city>
        <zip>49005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI of Neurology Psychiatry and Narcology NAMS</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kherson Regional Psychiatric Hospital</name>
      <address>
        <city>Kherson</city>
        <zip>73488</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyiv Regional Medical Incorporation Psychiatry</name>
      <address>
        <city>Kyiv</city>
        <zip>04080</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI of LOR Lviv Regional Clinical Psychiatric Hospital, Department #25</name>
      <address>
        <city>Lviv</city>
        <zip>79021</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution of Lviv Regional Council &quot;Lviv Regional Clinical Psychiatric Hospital&quot;, department #20</name>
      <address>
        <city>Lviv</city>
        <zip>79021</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odesa Regional Psychiatric Hospital 2</name>
      <address>
        <city>Odesa</city>
        <zip>67513</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maltsev Regional Clinical Psychiatric Hospital</name>
      <address>
        <city>Poltava</city>
        <zip>36013</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ternopil Regional Municipal Clinical Psychoneurological Hospital</name>
      <address>
        <city>Ternopil'</city>
        <zip>46027</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>O.I. Yushenko Vinnitsa Regional Clinic</name>
      <address>
        <city>Vinnitsa</city>
        <zip>21018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Croatia</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Romania</country>
  </removed_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>July 29, 2020</results_first_submitted>
  <results_first_submitted_qc>August 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2020</results_first_posted>
  <last_update_submitted>August 14, 2020</last_update_submitted>
  <last_update_submitted_qc>August 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bipolar</keyword>
  <keyword>Mania</keyword>
  <keyword>Brexpiprazole</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mania</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brexpiprazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.</ipd_time_frame>
    <ipd_access_criteria>Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com</ipd_access_criteria>
    <ipd_url>https://clinical-trials.otsuka.com</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03287869/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03287869/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study included participants who completed 3-week double-blind treatment in studies 331-201-00080 (NCT03259555)/331-201-00081 (NCT03257865) and, who in the investigator's judgment, could potentially benefit to receive brexpiprazole in this study. Data was summarized as per the treatment received in the previous studies.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Prior Brexpiprazole</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group.</description>
        </group>
        <group group_id="P2">
          <title>Prior Placebo</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="188"/>
                <participants group_id="P2" count="193"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Analyzed For Safety (Safety Sample)</title>
              <participants_list>
                <participants group_id="P1" count="184"/>
                <participants group_id="P2" count="184"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="105"/>
                <participants group_id="P2" count="100"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="83"/>
                <participants group_id="P2" count="93"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="12"/>
              </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="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance With Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Early Closure of the Site</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason not Specified</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Enrolled Sample included all participants who signed an inform consent form (ICF) for the trial.</population>
      <group_list>
        <group group_id="B1">
          <title>Prior Brexpiprazole</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group.</description>
        </group>
        <group group_id="B2">
          <title>Prior Placebo</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group.</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="188"/>
            <count group_id="B2" value="193"/>
            <count group_id="B3" value="381"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.6" spread="11.0"/>
                    <measurement group_id="B2" value="46.1" spread="11.5"/>
                    <measurement group_id="B3" value="45.8" spread="11.2"/>
                  </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="97"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="189"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="101"/>
                    <measurement group_id="B3" value="192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="129"/>
                    <measurement group_id="B2" value="146"/>
                    <measurement group_id="B3" value="275"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Race-Other</title>
                  <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_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="165"/>
                    <measurement group_id="B2" value="169"/>
                    <measurement group_id="B3" value="334"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ethnicity-Other</title>
                  <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_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity</title>
        <description>An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.</description>
        <time_frame>From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)</time_frame>
        <population>Safety Sample included all participants who received at least 1 dose of IMP (brexpiprazole).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior Brexpiprazole</title>
            <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group.</description>
          </group>
          <group group_id="O2">
            <title>Prior Placebo</title>
            <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity</title>
          <description>An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.</description>
          <population>Safety Sample included all participants who received at least 1 dose of IMP (brexpiprazole).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="184"/>
                <count group_id="O2" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAE, Any grade</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79"/>
                    <measurement group_id="O2" value="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE, Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE, Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE, Severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)</time_frame>
      <desc>Safety Sample included all participants who received at least 1 dose of IMP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Prior Brexpiprazole</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group.</description>
        </group>
        <group group_id="E2">
          <title>Prior Placebo</title>
          <description>Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (22.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="184"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo Positional</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="184"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="184"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Bipolar Disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="184"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Mania</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Suicidal Behaviour</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="184"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="184"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (22.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="184"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="184"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="184"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="184"/>
              </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>Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>As predefined in the protocol, there were no primary or secondary efficacy endpoints in this trial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Global Clinical Development</name_or_title>
      <organization>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</organization>
      <phone>1-609-524-6788</phone>
      <email>clinicaltransparency@otsuka-us.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03287869
org study id: 331-201-00083
secondary id: 2017-002225-38
nct id: NCT03287869
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study evaluated the safety and evaluate the safety and tolerability of open-label
      brexpiprazole (2 - 4 mg/day, with a starting dose of 2 mg/day) for the treatment of adult
      subjects with bipolar I disorder. All participants received a starting dose of brexpiprazole.
While the availability of atypical antipsychotics had increased the therapeutic options
      available, there remains a need for safer and more effective therapies in the treatment of
      manic and depressive episodes of bipolar I disorder. Brexpiprazole's specific receptor
      activity profile likely correlates with its established efficacy in schizophrenia and major
      depressive disorder, and may prove to be an effective target for the treatment of acute mania
      of bipolar I disorder.
intervention model: Parallel Assignment
intervention model description: Group composed of eligible rollover participants who completed one of the double-blind, phase 3 efficacy trials (331-201-00080 (NCT03259555) or 331-201-00081 (NCT03257865)).
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
time frame: From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
description: An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.
arm group label: Brexpiprazole
arm group type: Experimental
description: Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4.
intervention type: Drug
intervention name: Brexpiprazole
description: Brexpiprazole tablets
arm group label: Brexpiprazole
other name: OPC-34712
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Bulgaria
country: Croatia
country: Poland
country: Serbia
country: Ukraine
country: United States
country: Romania
responsible party type: Sponsor
mesh term: Mania
mesh term: Brexpiprazole
sharing ipd: Yes
ipd description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
ipd access criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
ipd url: https://clinical-trials.otsuka.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: As predefined in the protocol, there were no primary or secondary efficacy endpoints in this trial.
point of contact: 