<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/NCT02218008</url>
  </required_header>
  <id_info>
    <org_study_id>ALK5461-207</org_study_id>
    <nct_id>NCT02218008</nct_id>
  </id_info>
  <brief_title>A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - FORWARD-5 Study</brief_title>
  <official_title>A Phase 3 Efficacy and Safety Study of ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder (the FORWARD-5 Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alkermes, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alkermes, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the efficacy and safety of ALKS 5461.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</measure>
    <time_frame>Baseline and 5 weeks (Stage 1) and baseline and 6 weeks (Stage 2), combined together for the overall estimate of treatment effect</time_frame>
    <description>The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</measure>
    <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
    <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline to End of Treatment in the MADRS-10</measure>
    <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
    <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients Who Exhibited Treatment Response (MADRS-10)</measure>
    <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
    <description>The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 5). The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remission Rate</measure>
    <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
    <description>The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤10 at the end of the efficacy period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Adverse Events (AEs)</measure>
    <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">407</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALKS 5461</intervention_name>
    <description>Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a BMI of 18.0 to 40.0 kg/m2, inclusive&#xD;
&#xD;
          -  Agree to use an acceptable method of contraception for the duration of the study&#xD;
&#xD;
          -  Have an MDD primary diagnosis&#xD;
&#xD;
          -  Have no more than 2 inadequate responses to antidepressant therapy (ADT) in the&#xD;
             current Major Depressive Episode (MDE)&#xD;
&#xD;
          -  Additional criteria may apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have a current primary Axis-I disorder other than MDD&#xD;
&#xD;
          -  Have used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid&#xD;
             antagonists (eg, naloxone, naltrexone) within 14 days&#xD;
&#xD;
          -  Have received electroconvulsive therapy treatment within the last 2 years or received&#xD;
             more than one course of electroconvulsive treatment during their lifetime&#xD;
&#xD;
          -  Have attempted suicide within the past 2 years&#xD;
&#xD;
          -  Have a positive test for drugs of abuse&#xD;
&#xD;
          -  Are pregnant, planning to become pregnant, or breastfeeding&#xD;
&#xD;
          -  Have a history of intolerance, allergy, or hypersensitivity to buprenorphine or opioid&#xD;
             antagonists (eg, naltrexone, naloxone)&#xD;
&#xD;
          -  Have had a significant blood loss or blood donation within 60 days&#xD;
&#xD;
          -  Additional criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sanjeev Pathak, MD</last_name>
    <role>Study Director</role>
    <affiliation>Alkermes, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Colton</city>
        <state>California</state>
        <zip>92324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Pico Rivera</city>
        <state>California</state>
        <zip>90660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>San Gabriel</city>
        <state>California</state>
        <zip>91776</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Oakland Park</city>
        <state>Florida</state>
        <zip>33334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Winter Haven</city>
        <state>Florida</state>
        <zip>33880</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Smyrna</city>
        <state>Georgia</state>
        <zip>30080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Flowood</city>
        <state>Mississippi</state>
        <zip>39232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Saint Charles</city>
        <state>Missouri</state>
        <zip>63304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10168</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>High Point</city>
        <state>North Carolina</state>
        <zip>27265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>DeSoto</city>
        <state>Texas</state>
        <zip>75115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Wichita Falls</city>
        <state>Texas</state>
        <zip>76309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Clinton</city>
        <state>Utah</state>
        <zip>84015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Gatineau</city>
        <zip>J8T 8J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Halifax</city>
        <zip>B3S 1M7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Penticton</city>
        <zip>V2A 4M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Quebec</city>
        <zip>G3K 2P8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10245</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10629</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Hannover</city>
        <zip>30159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Oranienburg</city>
        <zip>16515</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Schwerin</city>
        <zip>19053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>Stralsund</city>
        <zip>18439</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>San Juan</city>
        <zip>00918</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alkermes Investigational Site</name>
      <address>
        <city>San Juan</city>
        <zip>00926</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <results_first_submitted>March 1, 2019</results_first_submitted>
  <results_first_submitted_qc>March 1, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 27, 2019</results_first_posted>
  <last_update_submitted>August 2, 2019</last_update_submitted>
  <last_update_submitted_qc>August 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Major depressive disorder (MDD)</keyword>
  <keyword>depression</keyword>
  <keyword>Alkermes</keyword>
  <keyword>ALKS 5461</keyword>
  <keyword>samidorphan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were diagnosed with major depressive disorder (MDD), and had an inadequate response to 1 or 2 adequate courses of treatment with a commercially available antidepressant therapy (ADT) during the current major depressive episode (MDE). All subjects continued ADT for the duration of the study.</recruitment_details>
      <pre_assignment_details>This was a Sequential Parallel Comparison Design (SPCD) study comprised of 2 stages. In Stage 1 subjects were randomized to ALKS 5461 or placebo (2:2:9). In Stage 2 only placebo non-responders from Stage 1 were re-randomized to ALKS 5461 or placebo (1:1:1). 1 subject randomized to the placebo group in Stage 1 did not receive any study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo S1</title>
          <description>Randomized to placebo in Stage 1</description>
        </group>
        <group group_id="P2">
          <title>ALKS 5461 1mg/1mg S1</title>
          <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
        </group>
        <group group_id="P3">
          <title>ALKS 5461 2mg/2mg S1</title>
          <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
        </group>
        <group group_id="P4">
          <title>Placebo S2</title>
          <description>Randomized to placebo in Stage 2</description>
        </group>
        <group group_id="P5">
          <title>ALKS 5461 1mg/1mg S2</title>
          <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
        </group>
        <group group_id="P6">
          <title>ALKS 5461 2mg/2mg S2</title>
          <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Stage 1 (S1)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="280"/>
                <participants group_id="P2" count="63"/>
                <participants group_id="P3" count="63"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="258"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="48"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance; drug use</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Failure to Meet Eligibility Criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Stage 2 (S2)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="62"/>
                <participants group_id="P5" count="62"/>
                <participants group_id="P6" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="58"/>
                <participants group_id="P5" count="58"/>
                <participants group_id="P6" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Failure to Meet Eligibility Criteria</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Randomized to placebo in Stage 1</description>
        </group>
        <group group_id="B2">
          <title>ALKS 5461 1mg/1mg</title>
          <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
        </group>
        <group group_id="B3">
          <title>ALKS 5461 2mg/2mg</title>
          <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="280"/>
            <count group_id="B2" value="63"/>
            <count group_id="B3" value="63"/>
            <count group_id="B4" value="406"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.7" spread="12.87"/>
                    <measurement group_id="B2" value="45.1" spread="11.46"/>
                    <measurement group_id="B3" value="42.9" spread="14.48"/>
                    <measurement group_id="B4" value="45.2" spread="12.93"/>
                  </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="193"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="277"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="129"/>
                  </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="48"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="232"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="54"/>
                    <measurement group_id="B4" value="339"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" 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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="95"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="207"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="301"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="229"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="52"/>
                    <measurement group_id="B4" value="335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</title>
        <description>The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).</description>
        <time_frame>Baseline and 5 weeks (Stage 1) and baseline and 6 weeks (Stage 2), combined together for the overall estimate of treatment effect</time_frame>
        <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS assessment in the respective stage.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</title>
          <description>The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).</description>
          <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS assessment in the respective stage.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="273"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="60"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.6" spread="0.34"/>
                    <measurement group_id="O2" value="-6.0" spread="0.74"/>
                    <measurement group_id="O3" value="-6.8" spread="0.75"/>
                    <measurement group_id="O4" value="-1.5" spread="0.65"/>
                    <measurement group_id="O5" value="-2.2" spread="0.67"/>
                    <measurement group_id="O6" value="-3.2" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Analysis was conducted for each stage separately and overall efficacy was based on combined stage analysis where stage-specific estimates were combined using pre-specified equal weights. Within each stage ALKS 5461 2mg/2mg was compared to placebo (i.e., ALKS 5461 2mg/2mg S1 vs Placebo S1; and ALKS 5461 2mg/2mg S2 vs Placebo S2. The pre-specified order of hypothesis tests was ALKS 5461 2/2 compared to placebo followed by ALKS 5461 1/1 compared to placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.018</p_value>
            <p_value_desc>Hypothesis tests were two-sided with an alpha of 0.05. Control of type 1 error inflation due to multiplicity was achieved by pre-specifying a fixed sequence for statistical tests.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <method_desc>ALKS 5461 was compared to pbo using stage-specific MMRM for MADRS-10 Change from Baseline. Model-derived estimates were combined using equal weights.</method_desc>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.7</ci_lower_limit>
            <ci_upper_limit>-0.3</ci_upper_limit>
            <estimate_desc>Estimates below zero favor ALKS 5461.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</title>
        <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
        <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
        <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)</title>
          <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
          <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="273"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="60"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.1" spread="0.48"/>
                    <measurement group_id="O2" value="-8.8" spread="1.05"/>
                    <measurement group_id="O3" value="-10.3" spread="1.06"/>
                    <measurement group_id="O4" value="-2.1" spread="0.88"/>
                    <measurement group_id="O5" value="-3.2" spread="0.91"/>
                    <measurement group_id="O6" value="-3.7" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Analysis was conducted for each stage separately and overall efficacy was based on combined stage analysis where stage-specific estimates were combined using pre-specified equal weights. Within each stage ALKS 5461 2mg/2mg was compared to placebo (i.e., ALKS 5461 2mg/2mg S1 vs Placebo S1; and ALKS 5461 2mg/2mg S2 vs Placebo S2. The pre-specified order of hypothesis tests was ALKS 5461 2/2 compared to placebo followed by ALKS 5461 1/1 compared to placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Hypothesis tests were two-sided with an alpha of 0.05. Control of type 1 error inflation due to multiplicity was achieved by pre-specifying a fixed sequence for statistical tests.</non_inferiority_desc>
            <p_value>0.026</p_value>
            <p_value_desc>ALKS 5461 was compared to pbo using stage-specific MMRM for MADRS-10 Change from Baseline. Model-derived estimates were combined using equal weights.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.6</ci_lower_limit>
            <ci_upper_limit>-0.2</ci_upper_limit>
            <estimate_desc>Estimates below zero favor ALKS 5461.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to End of Treatment in the MADRS-10</title>
        <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
        <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
        <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Treatment in the MADRS-10</title>
          <description>The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
          <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="273"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="60"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.2" spread="0.55"/>
                    <measurement group_id="O2" value="-10.3" spread="1.19"/>
                    <measurement group_id="O3" value="-10.8" spread="1.22"/>
                    <measurement group_id="O4" value="-1.9" spread="0.96"/>
                    <measurement group_id="O5" value="-3.4" spread="0.98"/>
                    <measurement group_id="O6" value="-3.6" spread="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>ALKS 5461 is compared to placebo within each of the 2 stages (i.e., ALKS 5461 2/2 S1 vs Placebo S1; and ALKS 5461 2/2 S2 vs Placebo S2). Efficacy was estimated as a weighted average across 2 stages using equal weights.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>The primary hypotheses were evaluated using a 6-step, fixed sequence approach to adjust for multiple comparisons. Using this method, hypothesis testing (using alpha=0.05) continued through the sequence until statistical significance was not achieved. Steps 1-3 included testing the ALKS 5461 2mg/2mg dose vs placebo for the 3 primary endpoints.</non_inferiority_desc>
            <p_value>0.076</p_value>
            <p_value_desc>ALKS 5461 is compared to placebo within each of the 2 stages, and resulting treatment effects from each stage are combined for a single hypothesis test using equal weights of 0.5 for both stages.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.6</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients Who Exhibited Treatment Response (MADRS-10)</title>
        <description>The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 5). The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
        <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
        <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients Who Exhibited Treatment Response (MADRS-10)</title>
          <description>The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 5). The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.</description>
          <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.</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="273"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="60"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="16"/>
                    <measurement group_id="O4" value="7"/>
                    <measurement group_id="O5" value="7"/>
                    <measurement group_id="O6" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="212"/>
                    <measurement group_id="O2" value="45"/>
                    <measurement group_id="O3" value="47"/>
                    <measurement group_id="O4" value="53"/>
                    <measurement group_id="O5" value="55"/>
                    <measurement group_id="O6" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Remission Rate</title>
        <description>The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤10 at the end of the efficacy period.</description>
        <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
        <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 (or HAM-D17) assessment in the respective stage.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Remission Rate</title>
          <description>The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤10 at the end of the efficacy period.</description>
          <population>Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 (or HAM-D17) assessment in the respective stage.</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="273"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="60"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="242"/>
                    <measurement group_id="O2" value="54"/>
                    <measurement group_id="O3" value="55"/>
                    <measurement group_id="O4" value="56"/>
                    <measurement group_id="O5" value="56"/>
                    <measurement group_id="O6" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Adverse Events (AEs)</title>
        <time_frame>5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)</time_frame>
        <population>The safety population includes all subjects who were randomized and received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo S1</title>
            <description>Randomized to placebo in Stage 1</description>
          </group>
          <group group_id="O2">
            <title>ALKS 5461 1mg/1mg S1</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
          </group>
          <group group_id="O3">
            <title>ALKS 5461 2mg/2mg S1</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
          </group>
          <group group_id="O4">
            <title>Placebo S2</title>
            <description>Randomized to placebo in Stage 2</description>
          </group>
          <group group_id="O5">
            <title>ALKS 5461 1mg/1mg S2</title>
            <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
          </group>
          <group group_id="O6">
            <title>ALKS 5461 2mg/2mg S2</title>
            <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Adverse Events (AEs)</title>
          <population>The safety population includes all subjects who were randomized and received at least 1 dose of study drug.</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="280"/>
                <count group_id="O2" value="63"/>
                <count group_id="O3" value="63"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="151"/>
                    <measurement group_id="O2" value="37"/>
                    <measurement group_id="O3" value="42"/>
                    <measurement group_id="O4" value="25"/>
                    <measurement group_id="O5" value="29"/>
                    <measurement group_id="O6" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 weeks for Stage 1 and 6 weeks for Stage 2</time_frame>
      <desc>The safety population includes all subjects who were randomized and received at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo S1</title>
          <description>Randomized to placebo in Stage 1</description>
        </group>
        <group group_id="E2">
          <title>ALKS 5461 1mg/1mg S1</title>
          <description>Randomized to ALKS 5461 1mg/1mg in Stage 1</description>
        </group>
        <group group_id="E3">
          <title>ALKS 5461 2mg/2mg S1</title>
          <description>Randomized to ALKS 5461 2mg/2mg in Stage 1</description>
        </group>
        <group group_id="E4">
          <title>Placebo S2</title>
          <description>Randomized to placebo in Stage 2</description>
        </group>
        <group group_id="E5">
          <title>ALKS 5461 1mg/1mg S2</title>
          <description>Randomized to ALKS 5461 1mg/1mg in Stage 2</description>
        </group>
        <group group_id="E6">
          <title>ALKS 5461 2mg/2mg S2</title>
          <description>Randomized to ALKS 5461 2mg/2mg in Stage 2</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-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="280"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="280"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="280"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wrist Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="280"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="280"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide Attempt</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="280"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="280"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="63"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="62"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="10" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="21" subjects_affected="20" subjects_at_risk="280"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="63"/>
                <counts group_id="E3" events="20" subjects_affected="17" subjects_at_risk="63"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="280"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="63"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="63"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="280"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="63"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="280"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E3" events="8" subjects_affected="7" subjects_at_risk="63"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="280"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="63"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="280"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="63"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="63"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="23" subjects_affected="22" subjects_at_risk="280"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="280"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="63"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </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>Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Eva Stroynowski</name_or_title>
      <organization>Alkermes, Inc.</organization>
      <phone>781-609-7000</phone>
      <email>eva.stroynowski@alkermes.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/NCT02218008
org study id: ALK5461-207
nct id: NCT02218008
lead sponsor: 
has dmc: No
This study will evaluate the efficacy and safety of ALKS 5461.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)
time frame: Baseline and 5 weeks (Stage 1) and baseline and 6 weeks (Stage 2), combined together for the overall estimate of treatment effect
description: The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).
measure: Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)
time frame: 5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
description: The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.
measure: Change From Baseline to End of Treatment in the MADRS-10
time frame: 5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
description: The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.
measure: Proportion of Patients Who Exhibited Treatment Response (MADRS-10)
time frame: 5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
description: The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 5). The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.
measure: Remission Rate
time frame: 5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
description: The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤10 at the end of the efficacy period.
measure: Number of Subjects With Adverse Events (AEs)
time frame: 5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
arm group label: High Dose
arm group type: Experimental
arm group label: Low Dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: ALKS 5461
description: Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
arm group label: High Dose
arm group label: Low Dose
intervention type: Drug
intervention name: Placebo
description: Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Sanjeev Pathak, MD
role: Study Director
affiliation: Alkermes, Inc.
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country: Canada
country: Germany
country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
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