<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/NCT03018340</url>
  </required_header>
  <id_info>
    <org_study_id>ACP-103-042</org_study_id>
    <nct_id>NCT03018340</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder (CLARITY)</brief_title>
  <official_title>A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ACADIA Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ACADIA Pharmaceuticals Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the efficacy of pimavanserin compared to placebo when given adjunctively to a&#xD;
      selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor&#xD;
      (SNRI) antidepressant as treatment of patients with Major Depressive Disorder (MDD) and an&#xD;
      inadequate response to antidepressant therapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">October 2018</completion_date>
  <primary_completion_date type="Actual">September 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Week 5 in the HAMD-17 Total Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in the SDS Total Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Sheehan Disability Scale is a 3-item patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Response and Remission Rates at the End of 5-week Treatment Period</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.&#xD;
Treatment response was defined as a reduction from Baseline in HAMD-17 total score of &gt;=50%.&#xD;
Remission was defined as a HAMD-17 total score &lt;=7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in CGI-S Total Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Clinical Global Impression-Severity Scale is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-I score denotes more severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CGI-I Score at Week 5</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in SF-12 Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores &gt;50 indicate better physical or mental health than the mean and scores &lt;50 indicate worse health. A higher score is indicative of a better health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in DAI-10 Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as &quot;True,&quot; and 4 items that a patient who is fully adherent would rate as &quot;False.&quot; Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in KSS Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from &quot;extremely alert&quot; (1) to &quot;very sleepy, great effort to keep awake, fighting sleep&quot; (9). Higher scores denote more drowsiness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in MGH-SFI Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains (&quot;interest in sex,&quot; &quot;sexual arousal,&quot; &quot;ability to achieve orgasm,&quot; &quot;ability to maintain erection&quot; [males only], and &quot;sexual satisfaction&quot;). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in BIS-11 Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 5 in SIS Score</measure>
    <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
    <description>The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">207</enrollment>
  <condition>Adjunctive Treatment of Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Pimavanserin 34 mg + SSRI/SNRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug- pimavanserin, 34 mg, taken as two 17 mg tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + SSRI/SNRI</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, taken as two tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimavanserin</intervention_name>
    <description>Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
    <arm_group_label>Pimavanserin 34 mg + SSRI/SNRI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, taken as two tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
    <arm_group_label>Placebo + SSRI/SNRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients, aged 18 years and above&#xD;
&#xD;
          2. A clinical diagnosis of major depressive disorder (MDD)&#xD;
&#xD;
          3. Is being treated with one of the following SSRI or SNRI antidepressants as&#xD;
             monotherapy:&#xD;
&#xD;
               -  Citalopram&#xD;
&#xD;
               -  Escitalopram&#xD;
&#xD;
               -  Paroxetine&#xD;
&#xD;
               -  Fluoxetine&#xD;
&#xD;
               -  Sertraline&#xD;
&#xD;
               -  Duloxetine&#xD;
&#xD;
               -  Venlafaxine&#xD;
&#xD;
               -  Desvenlafaxine&#xD;
&#xD;
               -  Venlafaxine XR&#xD;
&#xD;
          4. Has a history of inadequate response to antidepressant treatments&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has a psychotic disorder other than MDD&#xD;
&#xD;
          2. Patient has current evidence of a serious and/or unstable neurologic, cardiovascular,&#xD;
             respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder,&#xD;
             including cancer or malignancies, which would affect the patient's ability to&#xD;
             participate in the program&#xD;
&#xD;
          3. Patient has a history or symptoms of long QT syndrome&#xD;
&#xD;
        Patients will be evaluated at screening to ensure that all criteria for study participation&#xD;
        are met. Patients may be excluded from the study based on these assessments (and&#xD;
        specifically if it is determined that their baseline health and psychiatric condition do&#xD;
        not meet all pre-specified entry criteria).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UAB</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Woodland Research Northwest</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synergy San Diego</name>
      <address>
        <city>National City</city>
        <state>California</state>
        <zip>91950</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Partners, LLC</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schuster Medical Research Institute</name>
      <address>
        <city>Sherman Oaks</city>
        <state>California</state>
        <zip>91403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Viking Clinical Research</name>
      <address>
        <city>Temecula</city>
        <state>California</state>
        <zip>92591</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Clinical Research Medical Group</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNS Health care (Jacksonville)</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNS Health care (Orlando)</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>iResearch Atlanta</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alam Medical Research, INC</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Center for Psychiatric Research</name>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KUMC</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Clinical Trials</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altea Research</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hassman Research Institute</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manhattan Behavioral Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Finger Lakes Clinical Research</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuro-Behavioral Clinical Research</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPS Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rivus Wellness &amp; Research Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Research Network (Oregon)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPenn</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BTC of Lincoln</name>
      <address>
        <city>Lincoln</city>
        <state>Rhode Island</state>
        <zip>02865</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Clinical Trials, Inc.</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FutureSearch Trials of Dallas, L.P.</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UTSW</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pillar Clinical Research</name>
      <address>
        <city>Richardson</city>
        <state>Texas</state>
        <zip>75080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ericksen Research &amp; Development</name>
      <address>
        <city>Clinton</city>
        <state>Utah</state>
        <zip>84015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPC Research</name>
      <address>
        <city>Waukesha</city>
        <state>Wisconsin</state>
        <zip>53188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <results_first_submitted>September 6, 2019</results_first_submitted>
  <results_first_submitted_qc>October 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 14, 2019</results_first_posted>
  <last_update_submitted>October 25, 2019</last_update_submitted>
  <last_update_submitted_qc>October 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>Pimavanserin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT03018340/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT03018340/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In Stage 1, pts were randomized to pimavanserin or placebo (1:3). At the end of Stage 1, placebo pts not responding to treatment were rerandomized (1:1) in Stage 2; all other pts continued in Stage 2 the initial randomized treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pimavanserin 34 mg + SSRI/SNRI</title>
          <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study.&#xD;
Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
        <group group_id="P2">
          <title>Placebo + SSRI/SNRI</title>
          <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2.&#xD;
Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="155"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="125"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with study drug/procedure</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not further specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients randomized. Baseline measures are shown for Stage 1 baseline, as Stage 2 baseline included the subset of Stage 1 patients meeting re-randomization criteria.</population>
      <group_list>
        <group group_id="B1">
          <title>Pimavanserin 34 mg + SSRI/SNRI</title>
          <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
        <group group_id="B2">
          <title>Placebo + SSRI/SNRI</title>
          <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2.&#xD;
Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</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="52"/>
            <count group_id="B2" value="155"/>
            <count group_id="B3" value="207"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>18-40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="100"/>
                    <measurement group_id="B3" value="138"/>
                  </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="43"/>
                    <measurement group_id="B2" value="108"/>
                    <measurement group_id="B3" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="56"/>
                  </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="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="149"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 5 in the HAMD-17 Total Score</title>
        <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>FAS Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
FAS Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in the HAMD-17 Total Score</title>
          <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.</description>
          <population>FAS Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
FAS Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.9" spread="0.62"/>
                    <measurement group_id="O2" value="22.0" spread="0.34"/>
                    <measurement group_id="O3" value="20.3" spread="0.83"/>
                    <measurement group_id="O4" value="20.4" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.9" spread="1.14"/>
                    <measurement group_id="O2" value="-7.1" spread="0.55"/>
                    <measurement group_id="O3" value="-2.8" spread="0.75"/>
                    <measurement group_id="O4" value="-3.2" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>This is the primary statistical comparison for Stage 1 and Stage 2 combined.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0390</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in weighted MMRM LSMs</param_type>
            <param_value>-1.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.85</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.4</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in MMRM LSMs</param_type>
            <param_value>-4.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.09</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.1</ci_lower_limit>
            <ci_upper_limit>-1.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6940</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in MMRM LSMs</param_type>
            <param_value>0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.30</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.1</ci_lower_limit>
            <ci_upper_limit>3.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in the SDS Total Score</title>
        <description>The Sheehan Disability Scale is a 3-item patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in the SDS Total Score</title>
          <description>The Sheehan Disability Scale is a 3-item patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.365" spread="0.2996"/>
                    <measurement group_id="O2" value="6.519" spread="0.1716"/>
                    <measurement group_id="O3" value="5.753" spread="0.3314"/>
                    <measurement group_id="O4" value="5.747" spread="0.4191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.229" spread="0.4436"/>
                    <measurement group_id="O2" value="-2.026" spread="0.2233"/>
                    <measurement group_id="O3" value="-0.890" spread="0.2798"/>
                    <measurement group_id="O4" value="-0.507" spread="0.3288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Response and Remission Rates at the End of 5-week Treatment Period</title>
        <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.&#xD;
Treatment response was defined as a reduction from Baseline in HAMD-17 total score of &gt;=50%.&#xD;
Remission was defined as a HAMD-17 total score &lt;=7.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Response and Remission Rates at the End of 5-week Treatment Period</title>
          <description>The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.&#xD;
Treatment response was defined as a reduction from Baseline in HAMD-17 total score of &gt;=50%.&#xD;
Remission was defined as a HAMD-17 total score &lt;=7.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</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="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treatment responders Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="38"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Remission rate Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in CGI-S Total Score</title>
        <description>The Clinical Global Impression-Severity Scale is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-I score denotes more severe depression.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in CGI-S Total Score</title>
          <description>The Clinical Global Impression-Severity Scale is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-I score denotes more severe depression.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="0.09"/>
                    <measurement group_id="O2" value="4.4" spread="0.05"/>
                    <measurement group_id="O3" value="4.1" spread="0.16"/>
                    <measurement group_id="O4" value="4.1" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="0.21"/>
                    <measurement group_id="O2" value="-1.1" spread="0.10"/>
                    <measurement group_id="O3" value="-0.5" spread="0.13"/>
                    <measurement group_id="O4" value="-0.5" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CGI-I Score at Week 5</title>
        <description>The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>CGI-I Score at Week 5</title>
          <description>The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="127"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="0.17"/>
                    <measurement group_id="O2" value="2.8" spread="0.10"/>
                    <measurement group_id="O3" value="3.0" spread="0.18"/>
                    <measurement group_id="O4" value="3.1" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in SF-12 Score</title>
        <description>The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores &gt;50 indicate better physical or mental health than the mean and scores &lt;50 indicate worse health. A higher score is indicative of a better health state.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in SF-12 Score</title>
          <description>The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores &gt;50 indicate better physical or mental health than the mean and scores &lt;50 indicate worse health. A higher score is indicative of a better health state.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="151"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PCS baseline (BL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.587" spread="1.7918"/>
                    <measurement group_id="O2" value="48.783" spread="0.9845"/>
                    <measurement group_id="O3" value="46.945" spread="2.0961"/>
                    <measurement group_id="O4" value="48.994" spread="2.0596"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PCS change from BL to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.981" spread="1.1036"/>
                    <measurement group_id="O2" value="-0.726" spread="0.7095"/>
                    <measurement group_id="O3" value="-0.546" spread="1.4718"/>
                    <measurement group_id="O4" value="1.811" spread="1.2081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCS baseline (BL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.113" spread="1.2848"/>
                    <measurement group_id="O2" value="24.004" spread="0.6570"/>
                    <measurement group_id="O3" value="27.557" spread="1.4023"/>
                    <measurement group_id="O4" value="28.524" spread="1.5909"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCS change from BL to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.146" spread="1.9531"/>
                    <measurement group_id="O2" value="7.989" spread="0.8137"/>
                    <measurement group_id="O3" value="3.566" spread="1.5421"/>
                    <measurement group_id="O4" value="0.578" spread="1.4600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in DAI-10 Score</title>
        <description>The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as &quot;True,&quot; and 4 items that a patient who is fully adherent would rate as &quot;False.&quot; Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in DAI-10 Score</title>
          <description>The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as &quot;True,&quot; and 4 items that a patient who is fully adherent would rate as &quot;False.&quot; Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="0.61"/>
                    <measurement group_id="O2" value="4.4" spread="0.34"/>
                    <measurement group_id="O3" value="5.1" spread="0.68"/>
                    <measurement group_id="O4" value="4.8" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="0.56"/>
                    <measurement group_id="O2" value="0.5" spread="0.26"/>
                    <measurement group_id="O3" value="0.6" spread="0.66"/>
                    <measurement group_id="O4" value="0.3" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in KSS Score</title>
        <description>The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from &quot;extremely alert&quot; (1) to &quot;very sleepy, great effort to keep awake, fighting sleep&quot; (9). Higher scores denote more drowsiness.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in KSS Score</title>
          <description>The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from &quot;extremely alert&quot; (1) to &quot;very sleepy, great effort to keep awake, fighting sleep&quot; (9). Higher scores denote more drowsiness.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="0.19"/>
                    <measurement group_id="O2" value="6.6" spread="0.14"/>
                    <measurement group_id="O3" value="6.7" spread="0.29"/>
                    <measurement group_id="O4" value="6.1" spread="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.33"/>
                    <measurement group_id="O2" value="-0.4" spread="0.18"/>
                    <measurement group_id="O3" value="-0.5" spread="0.29"/>
                    <measurement group_id="O4" value="-0.2" spread="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in MGH-SFI Score</title>
        <description>The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains (&quot;interest in sex,&quot; &quot;sexual arousal,&quot; &quot;ability to achieve orgasm,&quot; &quot;ability to maintain erection&quot; [males only], and &quot;sexual satisfaction&quot;). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in MGH-SFI Score</title>
          <description>The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains (&quot;interest in sex,&quot; &quot;sexual arousal,&quot; &quot;ability to achieve orgasm,&quot; &quot;ability to maintain erection&quot; [males only], and &quot;sexual satisfaction&quot;). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.642" spread="0.1967"/>
                    <measurement group_id="O2" value="4.457" spread="0.1176"/>
                    <measurement group_id="O3" value="4.678" spread="0.2269"/>
                    <measurement group_id="O4" value="4.264" spread="0.2893"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.830" spread="0.1814"/>
                    <measurement group_id="O2" value="-0.155" spread="0.0807"/>
                    <measurement group_id="O3" value="-0.472" spread="0.1580"/>
                    <measurement group_id="O4" value="-0.183" spread="0.1085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in BIS-11 Score</title>
        <description>The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in BIS-11 Score</title>
          <description>The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.5" spread="1.53"/>
                    <measurement group_id="O2" value="70.0" spread="0.92"/>
                    <measurement group_id="O3" value="65.9" spread="1.79"/>
                    <measurement group_id="O4" value="70.3" spread="1.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="126"/>
                    <count group_id="O3" value="28"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.2" spread="1.10"/>
                    <measurement group_id="O2" value="-2.8" spread="0.72"/>
                    <measurement group_id="O3" value="-1.4" spread="0.87"/>
                    <measurement group_id="O4" value="1.7" spread="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 5 in SIS Score</title>
        <description>The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.</description>
        <time_frame>Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively</time_frame>
        <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + SSRI/SNRI, Stage 1</title>
            <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O3">
            <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
          <group group_id="O4">
            <title>Placebo + SSRI/SNRI, Stage 2</title>
            <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 5 in SIS Score</title>
          <description>The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.</description>
          <population>Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1.&#xD;
Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (BL)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="152"/>
                    <count group_id="O3" value="29"/>
                    <count group_id="O4" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.9" spread="2.04"/>
                    <measurement group_id="O2" value="38.8" spread="1.22"/>
                    <measurement group_id="O3" value="35.2" spread="2.45"/>
                    <measurement group_id="O4" value="36.6" spread="3.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from BL to Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="126"/>
                    <count group_id="O3" value="28"/>
                    <count group_id="O4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.4" spread="2.97"/>
                    <measurement group_id="O2" value="-10.8" spread="1.42"/>
                    <measurement group_id="O3" value="-4.8" spread="2.06"/>
                    <measurement group_id="O4" value="-6.6" spread="2.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>10 weeks</time_frame>
      <desc>Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2&#xD;
AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately.&#xD;
Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 1</title>
          <description>Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
        <group group_id="E2">
          <title>Placebo + SSRI/SNRI, Stage 1</title>
          <description>Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2.&#xD;
Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
        <group group_id="E3">
          <title>Pimavanserin 34 mg + SSRI/SNRI, Stage 2</title>
          <description>Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
        <group group_id="E4">
          <title>Placebo + SSRI/SNRI, Stage 2</title>
          <description>Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</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="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus bladder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</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="22" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="155"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="155"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" events="15" subjects_affected="14" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </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>Investigator may publish the study results, relative to their own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the Sponsor for review and comment. The sponsor has 60 days to review and comment.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Interpretation of Stage 2 results is limited by the reduced number of patients vs initial projections anticipated by the protocol.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Sr. Dir. Medical Information and Medical Communications</name_or_title>
      <organization>ACADIA Pharmaceuticals Inc.</organization>
      <phone>858-261-2897</phone>
      <email>medicalinformation@acadia-pharm.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/NCT03018340
org study id: ACP-103-042
nct id: NCT03018340
lead sponsor: 
has dmc: No
To assess the efficacy of pimavanserin compared to placebo when given adjunctively to a
      selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor
      (SNRI) antidepressant as treatment of patients with Major Depressive Disorder (MDD) and an
      inadequate response to antidepressant therapy
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline to Week 5 in the HAMD-17 Total Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.
measure: Change From Baseline to Week 5 in the SDS Total Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Sheehan Disability Scale is a 3-item patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.
measure: Treatment Response and Remission Rates at the End of 5-week Treatment Period
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.
Treatment response was defined as a reduction from Baseline in HAMD-17 total score of >=50%.
Remission was defined as a HAMD-17 total score <=7.
measure: Change From Baseline to Week 5 in CGI-S Total Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Clinical Global Impression-Severity Scale is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-I score denotes more severe depression.
measure: CGI-I Score at Week 5
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.
measure: Change From Baseline to Week 5 in SF-12 Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores >50 indicate better physical or mental health than the mean and scores <50 indicate worse health. A higher score is indicative of a better health state.
measure: Change From Baseline to Week 5 in DAI-10 Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as "True," and 4 items that a patient who is fully adherent would rate as "False." Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.
measure: Change From Baseline to Week 5 in KSS Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from "extremely alert" (1) to "very sleepy, great effort to keep awake, fighting sleep" (9). Higher scores denote more drowsiness.
measure: Change From Baseline to Week 5 in MGH-SFI Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains ("interest in sex," "sexual arousal," "ability to achieve orgasm," "ability to maintain erection" [males only], and "sexual satisfaction"). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.
measure: Change From Baseline to Week 5 in BIS-11 Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.
measure: Change From Baseline to Week 5 in SIS Score
time frame: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
description: The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.
arm group label: Pimavanserin 34 mg + SSRI/SNRI
arm group type: Experimental
description: Drug- pimavanserin, 34 mg, taken as two 17 mg tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
arm group label: Placebo + SSRI/SNRI
arm group type: Placebo Comparator
description: Placebo, taken as two tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
intervention type: Drug
intervention name: Pimavanserin
description: Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
arm group label: Pimavanserin 34 mg + SSRI/SNRI
intervention type: Other
intervention name: Placebo
description: Placebo, taken as two tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
arm group label: Placebo + SSRI/SNRI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Pimavanserin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Interpretation of Stage 2 results is limited by the reduced number of patients vs initial projections anticipated by the protocol.
point of contact: 