<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/NCT02970929</url>
  </required_header>
  <id_info>
    <org_study_id>SEP361-202</org_study_id>
    <secondary_id>2016-001556-21</secondary_id>
    <nct_id>NCT02970929</nct_id>
  </id_info>
  <brief_title>An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia</brief_title>
  <official_title>A 26-Week Open-label Safety and Tolerability Extension Study of SEP-363856 in Adult Subjects With Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sumitomo Pharma America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sumitomo Pharma America, 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>
      An extension study of safety and tolerability of SEP-363856 in adult subjects with&#xD;
      schizophrenia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 26 week, multiregional, open-label extension study designed to evaluate the&#xD;
      long-term safety and tolerability of SEP-363856 for the treatment of subjects with&#xD;
      schizophrenia who have completed the 4 week double-blind treatment phase of Study SEP361-201&#xD;
      (NCT02969382) Subjects received open-label SEP-363856 50 mg/day from Day 1 through Day 3, and&#xD;
      then received flexible dosing of SEP-363856 (25, 50, or 75 mg/day) for the rest of the trial.&#xD;
&#xD;
      No statistical hypothesis tests will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">January 29, 2019</completion_date>
  <primary_completion_date type="Actual">January 29, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation</measure>
    <time_frame>From first dose of study drug to last study visit (27 weeks)</time_frame>
    <description>Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Overall post Open-label Baseline treatment period (26 weeks)</time_frame>
    <description>Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Overall post Open-label Baseline treatment period (26 weeks)</time_frame>
    <description>The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</measure>
    <time_frame>From the time of clinical response to relapse or censor (one day after the last study drug dose)</time_frame>
    <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</measure>
    <time_frame>From the time of clinical response to relapse or censor (one day after the last study drug dose)</time_frame>
    <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology)</measure>
    <time_frame>Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)</time_frame>
    <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score</measure>
    <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
    <description>The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score</measure>
    <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
    <description>The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
    <description>The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms.&#xD;
Total score will be equal to the sum of the 10 items (range between 0 and 60).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201</measure>
    <time_frame>Week 26</time_frame>
    <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">157</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>SEP-363856</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SEP-363856</intervention_name>
    <description>One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks</description>
    <arm_group_label>SEP-363856</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subject must give written informed consent and privacy authorization prior to participation&#xD;
        in the study and able to comply with the protocol, in the opinion of the investigator.&#xD;
&#xD;
          -  Subject has completed Study SEP361 201 through Week 4&#xD;
&#xD;
          -  Subject has not taken any medication other than the study drug for the purpose of&#xD;
             controlling schizophrenia symptoms during Study SEP361 201.&#xD;
&#xD;
          -  Female subject must have a negative urine pregnancy test at Visit 7 of Study SEP361&#xD;
             201; females who are post-menopausal (defined as at least 12 months of spontaneous&#xD;
             amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will&#xD;
             be exempted from the pregnancy test.&#xD;
&#xD;
          -  Male subjects with female partner(s) of childbearing potential must agree to avoid&#xD;
             fathering a child and use acceptable methods of birth control from screening until at&#xD;
             least 30 days after the last study drug administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject answers &quot;yes&quot; to &quot;suicidal ideation&quot; Item 4 (active suicidal ideation with&#xD;
             some intent to act, without specific plan) or Item 5 (active suicidal ideation with&#xD;
             specific plan and intent) on the C-SSRS assessment at Visit 7 of Study SEP361 201.&#xD;
             Subjects who answer &quot;yes&quot; to this question must be referred to the Investigator for&#xD;
             follow up evaluation.&#xD;
&#xD;
          -  Subject has a clinically significant abnormality including physical examination, vital&#xD;
             signs, ECG, or laboratory test at Visit 7 of Study SEP361 201 that the investigator in&#xD;
             consultation with the medical monitor considers to be inappropriate to allow&#xD;
             participation in the study.&#xD;
&#xD;
          -  Subject has a positive urine drug screen (UDS) or breath alcohol test at Visit 7 of&#xD;
             Study SEP361 201.&#xD;
&#xD;
          -  Subject is pregnant or lactating.&#xD;
&#xD;
          -  Subject is at high risk of non-compliance in the Investigator's opinion.&#xD;
&#xD;
          -  Subject is in the opinion of the Investigator, unsuitable in any other way to&#xD;
             participate in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>CNS Medical Director</last_name>
    <role>Study Chair</role>
    <affiliation>Sumitomo Pharma America, 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>CNRI-Los Angeles, LLC</name>
      <address>
        <city>Pico Rivera</city>
        <state>California</state>
        <zip>90660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD Medical Center UCSD Department of Psychiatry</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103-8229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta Center for Medical Research</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kashinath Yadalam</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70629</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pillar Clinical Research, LLC</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bugát Pál Kórház-Rendelőintézet, Rehabilitációs Elmegyógyászati Osztály</name>
      <address>
        <city>Gyongyos</city>
        <state>Dózsa György</state>
        <zip>út 20-22</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza, Pszichiatriai Osztaly</name>
      <address>
        <city>Gyula</city>
        <zip>5700</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Universitar de Urgenta Militar Central &quot;Dr. Carol Davila&quot;</name>
      <address>
        <city>Bucuresti</city>
        <zip>010825</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrul de Evaluarea si Tratament al Toxicodependentelor pentru Tineri &quot;Sf. Stelian&quot;, Sectia Psihiatrie</name>
      <address>
        <city>Bucuresti</city>
        <zip>060222</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>spitalul Clinic de Neuropsihiatrie Craiova ,Clinica II Psihiatrie</name>
      <address>
        <city>Craiova</city>
        <zip>200473</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institutul de Psihiatrie Socola Iasi, Sectia Psihiatrie III Acuti</name>
      <address>
        <city>Iasi</city>
        <zip>700282</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sverdlov Regional Psychiatric Clinical Hospital</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St-Petersburg SHI Psychiatrical hospital #1 n.a. Kaschenko</name>
      <address>
        <city>Gatchina</city>
        <zip>188357</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPHI &quot;City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SHI Regional Clinical Psychiatry Hospital of St. Sofia</name>
      <address>
        <city>Saratov</city>
        <zip>410060</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBEI HE &quot;Smolensk State Medical University&quot; of the MoH of the RF</name>
      <address>
        <city>Smolensk</city>
        <zip>214019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Psychiatric Hospital of St. Nikolay Chudotvorets</name>
      <address>
        <city>St. Petersburg</city>
        <zip>190121</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FB=SBI&quot;Saint Petersburg Scientific and Research Psychoneurological Institute n.a. V.M. Bekhterev&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>192019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPb SBIH &quot;City Psychoneurological Dispensary #7 (with inpatient facilities)&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>198020</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Psychoneurological Hospital #3, Dept of Crisis Cond &amp; Primary Psych Episode #1</name>
      <address>
        <city>Ivano Frankivsk</city>
        <zip>76014</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Kharkiv RCPH#3 Center of Emerg PsychSI Inst of Neur, Psych &amp; Narc of NAMSU, Unit of Emergency Psychiatry and Narcology</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Kharkiv Regional Clinical Psychiatric Hospital #3, Psychiatric Department of Primary Psychotic Episod</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Kherson Regional Psychiatric Hospital of Kherson RC</name>
      <address>
        <city>Kherson, Vil Stepanivka</city>
        <zip>73488</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TMA Psychiatry in Kyiv Center of NT &amp; Rehabilitation of Psychotic Conditions</name>
      <address>
        <city>Kyiv</city>
        <zip>04080</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Odesa Regional Medical Center of Mental Health</name>
      <address>
        <city>Odesa</city>
        <zip>65006</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Cherkasy Regional Psychiatric Hospital of ChRC, Femail Dept #11, Male Dept #12</name>
      <address>
        <city>Smila</city>
        <zip>20708</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ternopil RCCPH Depts of Psychiatry #2 (m) &amp; Psychiatry #6 Ternopil I.ya. Gorbachevskyi SMU</name>
      <address>
        <city>Ternopil</city>
        <zip>46020</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Transcarpathian Regional Narcological Dispensary</name>
      <address>
        <city>Uzhgorod</city>
        <zip>88000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI O.I. Yuschenko VRPsH Depts #7 &amp; #10 M.I. Pyrogov VNMU</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <results_first_submitted>November 30, 2021</results_first_submitted>
  <results_first_submitted_qc>February 8, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 9, 2022</results_first_posted>
  <disposition_first_submitted>December 2, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>February 8, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 9, 2022</disposition_first_posted>
  <last_update_submitted>February 8, 2022</last_update_submitted>
  <last_update_submitted_qc>February 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT02970929/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>February 27, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT02970929/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Subjects received open-label SEP-363856 50 mg/day from Day 1 through Day 3, and then received flexible dosing of SEP-363856 (25, 50, or 75 mg/day) for the rest of the trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>SEP-363856</title>
          <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="157"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Subjects Who Received Study Medication</title>
              <participants_list>
                <participants group_id="P1" count="156"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="105"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>NON-COMPLIANCE WITH STUDY DRUG</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>INVESTIGATOR CONSIDERS SUBJECT CLINICALLY UNSTABLE, NOT APPROPRIATE FOR DISCHARGE TO AN OUTPATIENT</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>SPONSOR REQUEST THAT SUBJECT BE WITHDRAWN DUE TO POSITIVE DRUG RESULTS AND FOR THE SUBJECT'S SAFETY</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>LOST TO FOLLOWUP</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>MOVED OUT OF STATE</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>SEP-363856</title>
          <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="156"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="154"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.2" spread="6.03"/>
                  </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="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="136"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&gt;=18 - &lt;25 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=25 - &lt;=40 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Country</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hungary</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Romania</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Russia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ukraine</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>United States</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Double-blind Baseline BMI (Body Mass Index) Group</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;18.5 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=18.5 - &lt;25.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=25.0 - &lt;30.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=30.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Open-label Baseline BMI (Body Mass Index) Group</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;18.5 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=18.5 - &lt;25.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=25.0 - &lt;30.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=30.0 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Open-label Baseline Waist Circumference (cm)</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85.20" spread="13.467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Open-label Baseline BMI (Body Mass Index) (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.05" spread="3.890"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Open-label Baseline Weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75.32" spread="13.987"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Open-label Baseline Height (cm)</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="173.1" spread="7.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Double-blind Baseline Waist Circumference (cm)</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85.36" spread="13.508"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Double-blind Baseline BMI (Body Mass Index) (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.07" spread="3.863"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Double-blind Baseline Weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75.38" spread="13.873"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Double-blind Baseline Height (cm)</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="173.1" spread="7.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation</title>
        <description>Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation</description>
        <time_frame>From first dose of study drug to last study visit (27 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation</title>
          <description>Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall Adverse Events (AEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events (SAEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse Events leading to discontinuation from study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse Events leading to discontinuation of study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</title>
        <description>Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
        <time_frame>Overall post Open-label Baseline treatment period (26 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</title>
          <description>Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any suicidal ideation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any suicidal behavior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any suicidality</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</title>
        <description>The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
        <time_frame>Overall post Open-label Baseline treatment period (26 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)</title>
          <description>The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SI: Wish to be dead</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SI: Non-specific active suicidal thoughts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SI: Any methods (not plan) without intent to act</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SI: Some intent to act, without specific plan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SI: Specific plan and intent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SB: Preparatory acts or behavior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SB: Aborted attempt</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SB: Interrupted attempt</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SB: Actual attempt (non-fatal)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SB: Completed suicide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</title>
        <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
        <time_frame>From the time of clinical response to relapse or censor (one day after the last study drug dose)</time_frame>
        <population>Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.</population>
        <group_list>
          <group group_id="O1">
            <title>PBO-SEP</title>
            <description>Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
          <group group_id="O2">
            <title>SEP-SEP</title>
            <description>Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</title>
          <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
          <population>Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">insufficient number of participants with events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</title>
        <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
        <time_frame>From the time of clinical response to relapse or censor (one day after the last study drug dose)</time_frame>
        <population>Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.</population>
        <group_list>
          <group group_id="O1">
            <title>PBO-SEP</title>
            <description>Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
          <group group_id="O2">
            <title>SEP-SEP</title>
            <description>Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856</title>
          <description>Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.</description>
          <population>Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology)</title>
        <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
        <time_frame>Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)</time_frame>
        <population>Subjects with PANSS data missing at a particular time point did not contribute to the summary for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology)</title>
          <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
          <population>Subjects with PANSS data missing at a particular time point did not contribute to the summary for that time point.</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="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Score: DB BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.5" spread="7.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: OL BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.1" spread="15.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Wk 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.3" spread="12.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Chg from DB BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-41.8" spread="13.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Chg from OL BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.6" spread="15.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive SS: DB BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.7" spread="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive SS: OL BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8" spread="4.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive SS: Wk 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.2" spread="3.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive SS: Chg from DB BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.5" spread="4.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive SS: Chg from OL BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.3" spread="5.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative SS: DB BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.4" spread="4.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative SS: OL BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.3" spread="4.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative SS: Wk 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" spread="4.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative SS: Chg from DB BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.4" spread="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative SS: Chg from OL BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.2" spread="4.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gen-Psychopathology SS: DB BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.4" spread="5.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gen-Psychopathology SS: OL BLN Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.1" spread="7.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gen-Psychopathology SS: Wk 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.0" spread="6.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gen-Psychopathology SS: Chg from DB BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.9" spread="7.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gen-Psychopathology SS: Chg from OL BLN at Wk 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.2" spread="8.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score</title>
        <description>The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.</description>
        <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
        <population>Subjects with CGI-S score data missing at a particular time point did not contribute to the summary for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score</title>
          <description>The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.</description>
          <population>Subjects with CGI-S score data missing at a particular time point did not contribute to the summary for that time point.</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="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CGI-S Score: DB Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="0.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI-S Score: OL Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI-S Score: Week 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI-S Score: Change from DB Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CGI-S Score: Change from OL Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score</title>
        <description>The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.</description>
        <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
        <population>Subjects with BNSS total score data missing at a particular time point did not contribute to the summary for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score</title>
          <description>The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.</description>
          <population>Subjects with BNSS total score data missing at a particular time point did not contribute to the summary for that time point.</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="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Score: DB Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="148"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.4" spread="11.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: OL Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.0" spread="11.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Week 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5" spread="11.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Change from DB Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.8" spread="12.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Change from OL Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.3" spread="9.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</title>
        <description>The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms.&#xD;
Total score will be equal to the sum of the 10 items (range between 0 and 60).</description>
        <time_frame>Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26</time_frame>
        <population>Subjects with MADRS total score data missing at a particular time point did not contribute to the summary for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>SEP-363856</title>
            <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score</title>
          <description>The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms.&#xD;
Total score will be equal to the sum of the 10 items (range between 0 and 60).</description>
          <population>Subjects with MADRS total score data missing at a particular time point did not contribute to the summary for that time point.</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="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Score: DB Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" spread="7.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: OL Baseline Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="156"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" spread="6.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Week 26 Observed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="4.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Change from DB Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.1" spread="6.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score: Change from OL Baseline at Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.5" spread="5.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201</title>
        <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
        <time_frame>Week 26</time_frame>
        <population>Subjects who received at least one dose of open-label treatment and had PANSS total score data available at Double-blind Baseline and Week 26 are included in analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PBO-SEP</title>
            <description>Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
          <group group_id="O2">
            <title>SEP-SEP</title>
            <description>Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201</title>
          <description>PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.</description>
          <population>Subjects who received at least one dose of open-label treatment and had PANSS total score data available at Double-blind Baseline and Week 26 are included in analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug to last study visit (27 weeks)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SEP-363856</title>
          <description>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="156"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Acute psychosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="156"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="156"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="156"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="36" subjects_affected="18" subjects_at_risk="156"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="36" subjects_affected="8" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="13" subjects_at_risk="156"/>
              </event>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="156"/>
              </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>In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>CNS Medical Director</name_or_title>
      <organization>Sunovion Pharmaceuticals Inc.</organization>
      <phone>1 866-503-6351</phone>
      <email>clinicaltrialdisclosure@sunovion.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/NCT02970929
org study id: SEP361-202
secondary id: 2016-001556-21
nct id: NCT02970929
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
An extension study of safety and tolerability of SEP-363856 in adult subjects with
      schizophrenia
This is a 26 week, multiregional, open-label extension study designed to evaluate the
      long-term safety and tolerability of SEP-363856 for the treatment of subjects with
      schizophrenia who have completed the 4 week double-blind treatment phase of Study SEP361-201
      (NCT02969382) Subjects received open-label SEP-363856 50 mg/day from Day 1 through Day 3, and
      then received flexible dosing of SEP-363856 (25, 50, or 75 mg/day) for the rest of the trial.

      No statistical hypothesis tests will be performed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation
time frame: From first dose of study drug to last study visit (27 weeks)
description: Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation
measure: Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)
time frame: Overall post Open-label Baseline treatment period (26 weeks)
description: Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.
measure: Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)
time frame: Overall post Open-label Baseline treatment period (26 weeks)
description: The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.
measure: Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856
time frame: From the time of clinical response to relapse or censor (one day after the last study drug dose)
description: Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.
measure: Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856
time frame: From the time of clinical response to relapse or censor (one day after the last study drug dose)
description: Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.
measure: Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology)
time frame: Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)
description: PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.
measure: Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score
time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
description: The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.
measure: Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score
time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
description: The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.
measure: Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
description: The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms.
Total score will be equal to the sum of the 10 items (range between 0 and 60).
measure: Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201
time frame: Week 26
description: PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.
arm group label: SEP-363856
arm group type: Experimental
description: SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
intervention type: Drug
intervention name: SEP-363856
description: One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks
arm group label: SEP-363856
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: CNS Medical Director
role: Study Chair
affiliation: Sumitomo Pharma America, Inc.
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country: Hungary
country: Romania
country: Russian Federation
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 