<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/NCT01670019</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00037462</org_study_id>
    <nct_id>NCT01670019</nct_id>
  </id_info>
  <brief_title>Antidepressant Plus Asenapine Versus Antidepressant Plus Placebo for Depression</brief_title>
  <official_title>A Randomized, Blinded, Comparison of Asenapine and Placebo as Adjunctive Treatment in Patients With Non-Psychotic Major Depressive Disorder Incompletely Responsive to Antidepressant Monotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 6-week comparison of asenapine versus placebo as an add-on to ongoing&#xD;
      antidepressant treatment in patients with major depression who have not had a complete&#xD;
      therapeutic response to treatment with the antidepressant alone.&#xD;
&#xD;
      The investigators hypothesize that added asenapine will produce greater reductions in&#xD;
      depression than will added placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will undertake a 6-week, double-blind, randomized, parallel-group,&#xD;
      placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis&#xD;
      who have had an incomplete therapeutic response to treatment with an antidepressant&#xD;
      medication alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>Phase 4</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 MADRS Total Score</measure>
    <time_frame>Baseline, 6 weeks</time_frame>
    <description>The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Study Completion Rate</measure>
    <time_frame>6 weeks</time_frame>
    <description>The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Response Rate</measure>
    <time_frame>Baseline, 6 weeks</time_frame>
    <description>Clinical Response rate will be defined as the number of participants with a &gt; 50% reduction from baseline in MADRS total score.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Remission Rate</measure>
    <time_frame>6 weeks</time_frame>
    <description>Clinical Remission will be defined as the number of participants with a MADRS total score &lt; 7.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of Sustained Remission</measure>
    <time_frame>2, 4, 6 weeks</time_frame>
    <description>Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS &lt; 7) is present.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Major Depressive Disorder Without Psychotic Features</condition>
  <arm_group>
    <arm_group_label>Asenapine 5-20 mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo 1-4 tablets daily</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Asenapine 5-20 mg daily</intervention_name>
    <description>5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
    <arm_group_label>Asenapine 5-20 mg daily</arm_group_label>
    <other_name>SAPHRIS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo 1-4 tablets daily</intervention_name>
    <description>One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
    <arm_group_label>Placebo 1-4 tablets daily</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -130 male or female patients, 18-65 years of age, with:&#xD;
&#xD;
          1. DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by&#xD;
             the Mini-International Neuro-psychiatric Interview (MINI)&#xD;
&#xD;
          2. MADRS total score &gt; 20, and item 1 (Apparent Sadness) score &gt; 2 at enrollment and&#xD;
             randomization&#xD;
&#xD;
          3. Inadequate therapeutic response during their current depressive episode; an inadequate&#xD;
             therapeutic response will be defined as continued depressive psychopathology (see&#xD;
             criterion 2) following &gt; six weeks of therapy at adequate doses (according to the US&#xD;
             label) of any non-tricyclic, non-MAOI antidepressant medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Additional DSM-IV Axis I diagnoses other than Generalized Anxiety Disorder, Panic&#xD;
             Disorder with or without Agoraphobia, or Social Phobia within 6 months prior to&#xD;
             enrollment&#xD;
&#xD;
          2. DSM-IV Axis II diagnoses that significantly impact the current psychiatric status&#xD;
&#xD;
          3. Current MDD episode lasting &gt; 12 months&#xD;
&#xD;
          4. Electroconvulsive therapy within the preceding 6 months&#xD;
&#xD;
          5. Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior&#xD;
             to enrollment&#xD;
&#xD;
          6. Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or&#xD;
             dementia (MMSE &lt;24)&#xD;
&#xD;
          7. Risk of suicide as defined by MADRS item 10 score &gt; 4&#xD;
&#xD;
          8. Prior failure to respond to asenapine&#xD;
&#xD;
          9. Pregnancy or failure to use an acceptable form of birth control. Pregnancy as&#xD;
             determined by serum pregnancy test at baseline&#xD;
&#xD;
         10. Hepatic impairment and history of low WBC, by medical history and interview.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Beyer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgia Health Sciences University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Behavioral Care</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brody School of Medicine at East Carolina University</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Carolina Psychiatric Research Center</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>June 29, 2015</results_first_submitted>
  <results_first_submitted_qc>August 31, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 1, 2015</results_first_posted>
  <last_update_submitted>August 31, 2015</last_update_submitted>
  <last_update_submitted_qc>August 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Depression</keyword>
  <keyword>Antidepressant</keyword>
  <keyword>Antipsychotic</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asenapine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Asenapine 5-20 mg Daily</title>
          <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
        </group>
        <group group_id="P2">
          <title>Placebo 1-4 Tablets Daily</title>
          <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" 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="3"/>
                <participants group_id="P2" 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="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Asenapine 5-20 mg Daily</title>
          <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
        </group>
        <group group_id="B2">
          <title>Placebo 1-4 Tablets Daily</title>
          <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="46"/>
          </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="44.39" spread="11.34"/>
                    <measurement group_id="B2" value="45.87" spread="12.016"/>
                    <measurement group_id="B3" value="45.13" spread="11.59"/>
                  </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="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in MADRS Total Score</title>
        <description>The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
        <time_frame>Baseline, 6 weeks</time_frame>
        <population>Analysis includes those participants who completed week 6 assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Asenapine 5-20 mg Daily</title>
            <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo 1-4 Tablets Daily</title>
            <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
          </group>
        </group_list>
        <measure>
          <title>Change in MADRS Total Score</title>
          <description>The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
          <population>Analysis includes those participants who completed week 6 assessment.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.29" spread="9.73"/>
                    <measurement group_id="O2" value="-11.61" spread="11.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Study Completion Rate</title>
        <description>The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks</description>
        <time_frame>6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Asenapine 5-20 mg Daily</title>
            <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo 1-4 Tablets Daily</title>
            <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
          </group>
        </group_list>
        <measure>
          <title>Study Completion Rate</title>
          <description>The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.87"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Response Rate</title>
        <description>Clinical Response rate will be defined as the number of participants with a &gt; 50% reduction from baseline in MADRS total score.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
        <time_frame>Baseline, 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Asenapine 5-20 mg Daily</title>
            <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo 1-4 Tablets Daily</title>
            <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Response Rate</title>
          <description>Clinical Response rate will be defined as the number of participants with a &gt; 50% reduction from baseline in MADRS total score.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Remission Rate</title>
        <description>Clinical Remission will be defined as the number of participants with a MADRS total score &lt; 7.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
        <time_frame>6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Asenapine 5-20 mg Daily</title>
            <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo 1-4 Tablets Daily</title>
            <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Remission Rate</title>
          <description>Clinical Remission will be defined as the number of participants with a MADRS total score &lt; 7.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rates of Sustained Remission</title>
        <description>Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS &lt; 7) is present.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
        <time_frame>2, 4, 6 weeks</time_frame>
        <population>Participants that completed all data collection timepoints at week 2, 4, 6.</population>
        <group_list>
          <group group_id="O1">
            <title>Asenapine 5-20 mg Daily</title>
            <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo 1-4 Tablets Daily</title>
            <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
          </group>
        </group_list>
        <measure>
          <title>Rates of Sustained Remission</title>
          <description>Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS &lt; 7) is present.&#xD;
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.</description>
          <population>Participants that completed all data collection timepoints at week 2, 4, 6.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Asenapine 5-20 mg Daily</title>
          <description>Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability&#xD;
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID</description>
        </group>
        <group group_id="E2">
          <title>Placebo 1-4 Tablets Daily</title>
          <description>Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability&#xD;
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oral/ Lingual dysaethesia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>orthostasis faintness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Excessive daytime sedation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="23"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>John Beyer, M.D.</name_or_title>
      <organization>Duke University</organization>
      <phone>919-668-0209</phone>
      <email>john.beyer@dm.duke.edu</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/NCT01670019
org study id: Pro00037462
nct id: NCT01670019
lead sponsor: 
collaborator: 
has dmc: No
This is a 6-week comparison of asenapine versus placebo as an add-on to ongoing
      antidepressant treatment in patients with major depression who have not had a complete
      therapeutic response to treatment with the antidepressant alone.

      The investigators hypothesize that added asenapine will produce greater reductions in
      depression than will added placebo.
The investigators will undertake a 6-week, double-blind, randomized, parallel-group,
      placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis
      who have had an incomplete therapeutic response to treatment with an antidepressant
      medication alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in MADRS Total Score
time frame: Baseline, 6 weeks
description: The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy.
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
measure: Study Completion Rate
time frame: 6 weeks
description: The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks
measure: Clinical Response Rate
time frame: Baseline, 6 weeks
description: Clinical Response rate will be defined as the number of participants with a > 50% reduction from baseline in MADRS total score.
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
measure: Clinical Remission Rate
time frame: 6 weeks
description: Clinical Remission will be defined as the number of participants with a MADRS total score < 7.
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
measure: Rates of Sustained Remission
time frame: 2, 4, 6 weeks
description: Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS < 7) is present.
MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
arm group label: Asenapine 5-20 mg daily
arm group type: Experimental
description: Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability
arm group label: Placebo 1-4 tablets daily
arm group type: Placebo Comparator
description: Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability
intervention type: Drug
intervention name: Asenapine 5-20 mg daily
description: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID
arm group label: Asenapine 5-20 mg daily
other name: SAPHRIS
intervention type: Drug
intervention name: Placebo 1-4 tablets daily
description: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID
arm group label: Placebo 1-4 tablets daily
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: John Beyer, MD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Asenapine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 