<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/NCT03033069</url>
  </required_header>
  <id_info>
    <org_study_id>331-201-00061</org_study_id>
    <nct_id>NCT03033069</nct_id>
  </id_info>
  <brief_title>A Study of Flexible Dose Brexpiprazole as Monotherapy or Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder (PTSD)</brief_title>
  <official_title>A Phase 2, Multicenter, Randomized, Double-blind, Placebo- and Active-controlled Trial of Brexpiprazole (1 - 3 mg/Day) as Monotherapy or as Combination Therapy in the Treatment of Adults With Post-traumatic Stress 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 evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as&#xD;
      monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial is designed to assess the efficacy, safety and tolerability of flexible dose&#xD;
      brexpiprazole as monotherapy or as combination therapy with Zoloft (Sertraline) in adult&#xD;
      participants with PTSD.&#xD;
&#xD;
      This study will consist of a continuous 12-week, double-blind treatment period with a 14-day&#xD;
      follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 26, 2017</start_date>
  <completion_date type="Actual">November 12, 2018</completion_date>
  <primary_completion_date type="Actual">November 12, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">336</enrollment>
  <condition>Stress Disorders, Post-Traumatic</condition>
  <arm_group>
    <arm_group_label>Brexpiprazole + Sertraline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sertraline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole</intervention_name>
    <description>Brexpiprazole oral tablets.</description>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_label>Brexpiprazole + Sertraline</arm_group_label>
    <other_name>OPC-34712</other_name>
    <other_name>OPC-331</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <description>Sertraline oral capsules.</description>
    <arm_group_label>Brexpiprazole + Sertraline</arm_group_label>
    <arm_group_label>Sertraline</arm_group_label>
    <other_name>Zoloft</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brexpiprazole Matching Placebo</intervention_name>
    <description>Brexpiprazole matching placebo oral tablets.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sertraline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline Matching Placebo</intervention_name>
    <description>Sertraline matching placebo oral capsules.</description>
    <arm_group_label>Brexpiprazole</arm_group_label>
    <arm_group_label>Brexpiprazole + Sertraline</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sertraline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female participants between the years of 18-65 with a diagnosis of PTSD&#xD;
             (diagnosis can be made at screening)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Index trauma event &gt;15 years before screening&#xD;
&#xD;
          -  Index trauma event at age &lt;16&#xD;
&#xD;
          -  Any traumatic event within 3 months of screening&#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>Investigational Site</name>
      <address>
        <city>Tuscaloosa</city>
        <state>Alabama</state>
        <zip>35404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Bellflower</city>
        <state>California</state>
        <zip>90706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>National City</city>
        <state>California</state>
        <zip>91950</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Redlands</city>
        <state>California</state>
        <zip>92374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>San Marcos</city>
        <state>California</state>
        <zip>92078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30341</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Roswell</city>
        <state>Georgia</state>
        <zip>30076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Cedarhurst</city>
        <state>New York</state>
        <zip>11516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Salem</city>
        <state>Oregon</state>
        <zip>97301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Media</city>
        <state>Pennsylvania</state>
        <zip>19063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Norristown</city>
        <state>Pennsylvania</state>
        <zip>19403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Lincoln</city>
        <state>Rhode Island</state>
        <zip>02865</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Bellaire</city>
        <state>Texas</state>
        <zip>77401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Wichita Falls</city>
        <state>Texas</state>
        <zip>76309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>October 8, 2021</results_first_submitted>
  <results_first_submitted_qc>November 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 8, 2021</results_first_posted>
  <disposition_first_submitted>October 9, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>November 10, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 8, 2021</disposition_first_posted>
  <last_update_submitted>November 10, 2021</last_update_submitted>
  <last_update_submitted_qc>November 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sertraline</mesh_term>
    <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 the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/</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>June 8, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03033069/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>November 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03033069/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 48 investigative sites in the United States from 26 January 2017 to 12 November 2018.</recruitment_details>
      <pre_assignment_details>Of the 336 participants enrolled in the study, 321 participants diagnosed with post-traumatic stress disorder (PTSD) were randomized in 1:1:1:1 ratio to receive brexpiprazole monotherapy, brexpiprazole plus sertraline combination therapy, sertraline monotherapy or placebo up to Week 12.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Brexpiprazole + Sertraline</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="P2">
          <title>Brexpiprazole</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.</description>
        </group>
        <group group_id="P3">
          <title>Sertraline</title>
          <description>Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="82"/>
                <participants group_id="P2" count="75"/>
                <participants group_id="P3" count="81"/>
                <participants group_id="P4" count="83"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Sample</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="75"/>
                <participants group_id="P3" count="79"/>
                <participants group_id="P4" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent to Treat (ITT) Sample</title>
              <participants_list>
                <participants group_id="P1" count="79"/>
                <participants group_id="P2" count="72"/>
                <participants group_id="P3" count="77"/>
                <participants group_id="P4" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="50"/>
                <participants group_id="P3" count="59"/>
                <participants group_id="P4" count="64"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="22"/>
                <participants group_id="P4" count="19"/>
              </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="7"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </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="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal By Caregiver</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason not Specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Randomized Sample included all participants randomized into this trial.</population>
      <group_list>
        <group group_id="B1">
          <title>Brexpiprazole + Sertraline</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="B2">
          <title>Brexpiprazole</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.</description>
        </group>
        <group group_id="B3">
          <title>Sertraline</title>
          <description>Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week12.</description>
        </group>
        <group group_id="B5">
          <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="82"/>
            <count group_id="B2" value="75"/>
            <count group_id="B3" value="81"/>
            <count group_id="B4" value="83"/>
            <count group_id="B5" value="321"/>
          </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="38.4" spread="11.9"/>
                    <measurement group_id="B2" value="39.3" spread="10.6"/>
                    <measurement group_id="B3" value="38.6" spread="10.9"/>
                    <measurement group_id="B4" value="40.3" spread="11.0"/>
                    <measurement group_id="B5" value="39.2" spread="11.1"/>
                  </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="51"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="51"/>
                    <measurement group_id="B4" value="48"/>
                    <measurement group_id="B5" value="199"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="35"/>
                    <measurement group_id="B5" value="122"/>
                  </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>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="26"/>
                    <measurement group_id="B5" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="53"/>
                    <measurement group_id="B4" value="46"/>
                    <measurement group_id="B5" value="197"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="22"/>
                  </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="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="69"/>
                    <measurement group_id="B5" value="271"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="81"/>
                    <measurement group_id="B4" value="83"/>
                    <measurement group_id="B5" value="321"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score</title>
        <description>CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT Sample included all participants who were randomized in the trial and took at least one dose of double-blind investigational medicinal product (IMP) and have a Baseline and at least one post Baseline evaluation for the CAPS-5 total score. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Brexpiprazole + Sertraline</title>
            <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
          </group>
          <group group_id="O2">
            <title>Brexpiprazole</title>
            <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.</description>
          </group>
          <group group_id="O3">
            <title>Sertraline</title>
            <description>Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score</title>
          <description>CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.</description>
          <population>ITT Sample included all participants who were randomized in the trial and took at least one dose of double-blind investigational medicinal product (IMP) and have a Baseline and at least one post Baseline evaluation for the CAPS-5 total score. Overall number of participants analyzed are the number of participants with data available for analyses.</population>
          <units>score 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="59"/>
                <count group_id="O2" value="48"/>
                <count group_id="O3" value="58"/>
                <count group_id="O4" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.4" spread="1.43"/>
                    <measurement group_id="O2" value="-12.2" spread="1.57"/>
                    <measurement group_id="O3" value="-11.4" spread="1.46"/>
                    <measurement group_id="O4" value="-10.5" spread="1.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>MMRM analysis with an unstructured (UN) variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.0021</p_value>
            <method>Mixed Model Repeated Measures (MMRM)</method>
            <param_type>Least Squares (LS ) Mean Difference</param_type>
            <param_value>-5.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.79</ci_lower_limit>
            <ci_upper_limit>-2.19</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.3868</p_value>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-1.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.70</ci_lower_limit>
            <ci_upper_limit>2.22</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.6399</p_value>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.74</ci_lower_limit>
            <ci_upper_limit>2.92</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.0106</p_value>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-5.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.96</ci_lower_limit>
            <ci_upper_limit>-1.20</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.0384</p_value>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-4.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.26</ci_lower_limit>
            <ci_upper_limit>-0.23</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of the study drug up to 14 days after the last dose (Up to Week 14)</time_frame>
      <desc>Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Brexpiprazole + Sertraline</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="E2">
          <title>Brexpiprazole</title>
          <description>Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.</description>
        </group>
        <group group_id="E3">
          <title>Sertraline</title>
          <description>Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.</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="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Animal bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="47" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="46" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="43" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight increase</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anorgasmia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Delayed ejaculation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Contact</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="82"/>
              </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/NCT03033069
org study id: 331-201-00061
nct id: NCT03033069
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as
      monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD.
This trial is designed to assess the efficacy, safety and tolerability of flexible dose
      brexpiprazole as monotherapy or as combination therapy with Zoloft (Sertraline) in adult
      participants with PTSD.

      This study will consist of a continuous 12-week, double-blind treatment period with a 14-day
      follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score
time frame: Baseline, Week 12
description: CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.
arm group label: Brexpiprazole + Sertraline
arm group type: Experimental
description: Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.
arm group label: Brexpiprazole
arm group type: Experimental
description: Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.
arm group label: Sertraline
arm group type: Active Comparator
description: Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
intervention type: Drug
intervention name: Brexpiprazole
description: Brexpiprazole oral tablets.
arm group label: Brexpiprazole
arm group label: Brexpiprazole + Sertraline
other name: OPC-34712
other name: OPC-331
intervention type: Drug
intervention name: Sertraline
description: Sertraline oral capsules.
arm group label: Brexpiprazole + Sertraline
arm group label: Sertraline
other name: Zoloft
intervention type: Drug
intervention name: Brexpiprazole Matching Placebo
description: Brexpiprazole matching placebo oral tablets.
arm group label: Placebo
arm group label: Sertraline
intervention type: Drug
intervention name: Sertraline Matching Placebo
description: Sertraline matching placebo oral capsules.
arm group label: Brexpiprazole
arm group label: Brexpiprazole + Sertraline
arm group label: Placebo
arm group label: Sertraline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
mesh term: Sertraline
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 the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
ipd url: https://clinical-trials.otsuka.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 