<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/NCT03259555</url>
  </required_header>
  <id_info>
    <org_study_id>331-201-00080</org_study_id>
    <nct_id>NCT03259555</nct_id>
  </id_info>
  <brief_title>A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind Trial of Brexpiprazole Versus Placebo for the Acute Treatment of Manic Episodes, With or Without Mixed Features, Associated 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>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To demonstrate the efficacy of brexpiprazole for the acute treatment of manic episodes, with&#xD;
      or without mixed features, in participants with a diagnosis of bipolar I disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A multicenter, randomized, double-blind trial of brexpiprazole versus placebo for the acute&#xD;
      treatment of manic episodes, with or without mixed features, associated with bipolar I&#xD;
      disorder. This study also demonstrated the safety and tolerability of brexpiprazole in the&#xD;
      study population of males and females aged 18 to 65 years (inclusive, at time of consent).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 14, 2017</start_date>
  <completion_date type="Actual">January 2, 2019</completion_date>
  <primary_completion_date type="Actual">January 2, 2019</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>
    <intervention_model_description>Participants received a dose of brexpiprazole or placebo for a maximum of 21 days and were evaluated throughout the duration of the study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3</measure>
    <time_frame>Baseline, Week 3</time_frame>
    <description>The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the &quot;best&quot; rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3</measure>
    <time_frame>Baseline, Week 3</time_frame>
    <description>The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">322</enrollment>
  <condition>Bipolar I Disorder</condition>
  <condition>Manic Episode</condition>
  <arm_group>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received a starting dose of 2 milligrams (mg)/day brexpiprazole from Days 1 to 3, 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>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo was administered in the same way as brexpiprazole to maintain the blind.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.</description>
    <arm_group_label>Brexpiprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered orally daily for 3 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female participants, ages 18 to 65 years, inclusive, at the time of informed&#xD;
             consent.&#xD;
&#xD;
          -  Participants willing to discontinue all prohibited medications to meet&#xD;
             protocol-required washouts prior to and during the trial period.&#xD;
&#xD;
          -  Participants with a Diagnostic &amp; Statistical Manual on Mental Disorders, 5th Edition&#xD;
             (DSM-5) diagnosis of bipolar I disorder displaying an acute manic episode with or&#xD;
             without mixed features requiring hospitalization. Diagnosis confirmed by the MINI&#xD;
             International Neuropsychiatric Interview and a history of at least 1 previous manic&#xD;
             episode with or without mixed features with manic symptoms of sufficient severity to&#xD;
             require one of the following interventions: hospitalization or treatment with a mood&#xD;
             stabilizer, or treatment with an antipsychotic agent. &quot;Require&quot; was defined as an&#xD;
             intervention that occurred rather than one that was recommended.&#xD;
&#xD;
          -  Young-mania rating scale (YMRS) score of ≥24 at screening and baseline.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Sexually active male or women of childbearing potential who did not agree to practice&#xD;
             2 different methods of birth control or remain abstinent during the trial and for 30&#xD;
             days after the last dose of investigational medicinal product.&#xD;
&#xD;
          -  Females who were breastfeeding and/or who had a positive pregnancy test result prior&#xD;
             to receiving trial medication.&#xD;
&#xD;
          -  Participants considered unresponsive to clozapine or who were only responsive to&#xD;
             clozapine.&#xD;
&#xD;
          -  Participants with a history of DSM-5 diagnosis other than bipolar I disorder,&#xD;
             including schizophrenia, schizoaffective disorder, major depressive disorder,&#xD;
             attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other&#xD;
             cognitive disorders. Also, participants with borderline, paranoid, histrionic,&#xD;
             schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses&#xD;
             must have been discussed with the medical monitor.&#xD;
&#xD;
          -  Participants whose current manic episode had lasted for more than 4 weeks overall, or&#xD;
             who had required hospitalization &gt;21 days for the current acute episode at the time of&#xD;
             the screening visit, excluding hospitalization for psychosocial reasons.&#xD;
&#xD;
          -  Participant with manic symptoms better accounted for by another general medical&#xD;
             condition or direct physiological effect of substance (for example, medication).&#xD;
&#xD;
          -  Participants who have had electroconvulsive treatment within the past 2 months.&#xD;
&#xD;
          -  Participants with a positive drug screen for cocaine or other illicit drugs.&#xD;
&#xD;
          -  Abnormal laboratory test results, vital signs or electrocardiogram findings, unless&#xD;
             based on investigator's judgment the findings are not medically significant or would&#xD;
             not impact the safety of the participant or the interpretation of the trial results.&#xD;
&#xD;
          -  Rapid cyclers with more than 6 episodes in the previous year.&#xD;
&#xD;
          -  Participants with hypothyroidism or hyperthyroidism (unless condition has been&#xD;
             stabilized with medications for at least the past 90 days) or an abnormal result for&#xD;
             free thyroxine at screening.&#xD;
&#xD;
          -  Participants with uncontrolled hypertension or symptomatic hypotension or orthostatic&#xD;
             hypotension.&#xD;
&#xD;
          -  Participant with epilepsy or history of seizures.&#xD;
&#xD;
          -  Participants who participated in a clinical trial within the last 60 days or who&#xD;
             participated in more than 2 clinical trials within the past year.&#xD;
&#xD;
          -  Use of psychotropic medications (other than benzodiazepines) within 7 days of the&#xD;
             baseline YMRS.&#xD;
&#xD;
          -  Participants who currently had clinically significant neurological, hepatic, renal,&#xD;
             metabolic, hematological, immunological, cardiovascular, pulmonary, or&#xD;
             gastrointestinal disorders.&#xD;
&#xD;
          -  Participants who received brexpiprazole in any prior clinical trial or currently&#xD;
             taking commercially available brexpiprazole (Rexulti).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Leoni, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</affiliation>
  </overall_official>
  <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>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>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</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>92506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Vista Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</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>Advanced Research Institute of Miami</name>
      <address>
        <city>Homestead</city>
        <state>Florida</state>
        <zip>33030</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>Optimus U Corporation</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Behavioral Clinical Research, Inc.</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Segal Trials</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research Inc.</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30325</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>CBH Health</name>
      <address>
        <city>Gaithersburg</city>
        <state>Maryland</state>
        <zip>20877</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Clinical Research Center, LLC</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richard H Weisler, MD, PA, and 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>Carolina Clinical Trials, Inc.</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas at Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78712</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>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>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</name>
      <address>
        <city>Burgas</city>
        <zip>8000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatry Hospital - Kardzhali</name>
      <address>
        <city>Kardzhali</city>
        <zip>6600</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatry Hospital Sv. Ivan Rilski</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</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center - Ruse EOOD</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</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment - Targovishte AD</name>
      <address>
        <city>Targovishte</city>
        <zip>7700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center - Veliko Tarnovo EOOD</name>
      <address>
        <city>Veliko Tarnovo</city>
        <zip>5000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center - Vratsa EOOD</name>
      <address>
        <city>Vratsa</city>
        <zip>3000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej im. Dr. Stanislawa Deresza w Choroszczy</name>
      <address>
        <city>Choroszcz</city>
        <zip>16-070</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Psychiatrii Doroslych</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Medyczne HCP Sp. z o. o.</name>
      <address>
        <city>Poznań</city>
        <zip>61-485</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>Clinic for Psychiatric Disorders Dr Laza Lazarevic</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Hospital Center Dr Dragisa Misovic-Dedinje</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Special Hospital for Psychiatric Diseases Kovin</name>
      <address>
        <city>Kovin</city>
        <zip>26220</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Kragujevac</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Vojvodina</name>
      <address>
        <city>Novi Sad</city>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <results_first_submitted>December 13, 2019</results_first_submitted>
  <results_first_submitted_qc>February 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 10, 2020</results_first_posted>
  <last_update_submitted>February 3, 2020</last_update_submitted>
  <last_update_submitted_qc>February 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brexpiprazole</keyword>
  <keyword>Bipolar</keyword>
  <keyword>Manic episode</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mania</mesh_term>
    <mesh_term>Bipolar Disorder</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>
  </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>December 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03259555/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 11, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03259555/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The trial population consisted of adult participants (18 to 65 years) diagnosed with bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Brexpiprazole</title>
          <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="158"/>
                <participants group_id="P2" count="164"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received At Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="158"/>
                <participants group_id="P2" count="163"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="124"/>
                <participants group_id="P2" count="134"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance With Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline population consisted of all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Brexpiprazole</title>
          <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.</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="158"/>
            <count group_id="B2" value="164"/>
            <count group_id="B3" value="322"/>
          </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="43.4" spread="11.7"/>
                    <measurement group_id="B2" value="44.5" spread="11.2"/>
                    <measurement group_id="B3" value="44.0" spread="11.5"/>
                  </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="80"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="163"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="159"/>
                  </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>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="141"/>
                    <measurement group_id="B2" value="141"/>
                    <measurement group_id="B3" value="282"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ethnicity - Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                    <measurement group_id="B2" value="113"/>
                    <measurement group_id="B3" value="208"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="105"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3</title>
        <description>The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the &quot;best&quot; rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM).</description>
        <time_frame>Baseline, Week 3</time_frame>
        <population>Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole</title>
            <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3</title>
          <description>The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the &quot;best&quot; rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM).</description>
          <population>Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.</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="124"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.6" spread="0.72"/>
                    <measurement group_id="O2" value="-10.8" spread="0.70"/>
                  </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</non_inferiority_type>
            <p_value>=0.8797</p_value>
            <method>Mixed-effect Model Repeated Measure</method>
            <method_desc>An &quot;unstructured&quot; covariance was used.</method_desc>
            <param_type>Treatment difference</param_type>
            <param_value>0.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.74</ci_lower_limit>
            <ci_upper_limit>2.03</ci_upper_limit>
            <estimate_desc>Comparison between treatment groups was carried out using MMRM, with study center, treatment group, visit, and treatment group-by-visit interaction as factor and baseline-by-visit interaction as a covariate. An &quot;unstructured&quot; covariance was used.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3</title>
        <description>The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.</description>
        <time_frame>Baseline, Week 3</time_frame>
        <population>Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole</title>
            <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3</title>
          <description>The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.</description>
          <population>Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.</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="124"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.12" spread="1.06"/>
                    <measurement group_id="O2" value="-1.21" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Brexpiprazole</title>
          <description>Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDra 21.1</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="158"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Dystonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mania</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDra 21.1</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="20" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="158"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="158"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="158"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="158"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="163"/>
              </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>
    <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/NCT03259555
org study id: 331-201-00080
nct id: NCT03259555
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To demonstrate the efficacy of brexpiprazole for the acute treatment of manic episodes, with
      or without mixed features, in participants with a diagnosis of bipolar I disorder.
A multicenter, randomized, double-blind trial of brexpiprazole versus placebo for the acute
      treatment of manic episodes, with or without mixed features, associated with bipolar I
      disorder. This study also demonstrated the safety and tolerability of brexpiprazole in the
      study population of males and females aged 18 to 65 years (inclusive, at time of consent).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants received a dose of brexpiprazole or placebo for a maximum of 21 days and were evaluated throughout the duration of the study.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
time frame: Baseline, Week 3
description: The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the "best" rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM).
measure: Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
time frame: Baseline, Week 3
description: The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.
arm group label: Brexpiprazole
arm group type: Experimental
description: Participants received a starting dose of 2 milligrams (mg)/day brexpiprazole from Days 1 to 3, 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo was administered in the same way as brexpiprazole to maintain the blind.
intervention type: Drug
intervention name: Brexpiprazole
description: Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.
arm group label: Brexpiprazole
intervention type: Drug
intervention name: Placebo
description: Administered orally daily for 3 weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Matthew Leoni, M.D.
role: Study Director
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
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country: Bulgaria
country: Poland
country: Serbia
country: United States
responsible party type: Sponsor
mesh term: Mania
mesh term: Bipolar Disorder
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
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certain agreements: 
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