<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT02970305</url>
  </required_header>
  <id_info>
    <org_study_id>ACP-103-038</org_study_id>
    <secondary_id>2016-003436-20</secondary_id>
    <nct_id>NCT02970305</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE)</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive&#xD;
      placebo in the treatment of the negative symptoms of schizophrenia&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 4, 2016</start_date>
  <completion_date type="Actual">October 28, 2019</completion_date>
  <primary_completion_date type="Actual">October 16, 2019</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 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on 4 main areas i.e. (a) socially useful activities, including work and study; (2) personal and social relationships, (3) self-care; and (4) disturbing and aggressive behaviors. The time period assessed is &quot;past month&quot;. Higher scores denote better psychosocial functioning</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.&#xD;
NSA-16 responders were defined as patients with at least 20, 30, 50, or 75% percentage improvement in NSA-16 total score from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The global negative symptoms rating of the NSA-16 assesses overall severity on a 7-point scale from 1 to 7, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores</measure>
    <time_frame>From baseline (BL) to Week 26</time_frame>
    <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The CGI-SCH-S is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The CGI-SCH-I is a clinician-rated, 7-point scale to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The score could range from 1 (very much improved) to 7 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The 7-point scores range from 1 (very much improved) to 7 (very much worse); responders were defined as those with CGI-SCH-I of 1 or 2.&#xD;
The analysis includes observed cases; missing cases were not imputed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score is the sum of scores and ranges from a minimum of 30 to a maximum of 210. Higher scores denote more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores</measure>
    <time_frame>From baseline (BL) to Week 26</time_frame>
    <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS has 3 subscales that are the sums of the respective item scores, including the positive scale (min 7, max 49), negative scale (min 7, max 49), and general psychopathology scale (min 16, max 112). Higher scores denote more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The BACS is a performance-based assessment of treatment-related changes in cognition, assessing 6 domains of verbal memory and learning; working memory; motor function; verbal fluency; attention and speed of processing; and executive function. The 6 domains with their raw scores are: verbal memory 0-75; digit sequencing 0-28; token motor 0-100; verbal fluency 0-225; symbol coding 0-110; Tower of London 0-22. For each domain, higher scores reflect better cognition. Raw scores are converted to age and sex-corrected normalized scores. The BACS composite score is calculated as the mean of the normalized scores from the 6 subscale scores, standardized so that the mean of the BACS composite score in the healthy normative sample is 50 and the standard deviation is 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a subject who is fully adherent to the prescribed medication would answer as &quot;True&quot; and 4 items (2, 5, 6, and 8) that a subject who is fully adherent to the prescribed medication would answer as &quot;False.&quot; A correct answer is scored +1 and an incorrect answer is scored -1. The total score is the sum of pluses and minuses, which can range from -10 to 10 in increments of 2. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (non-adherent). Higher scores denote better adherence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score</measure>
    <time_frame>From baseline to Week 26</time_frame>
    <description>The KSS is a self-reported subjective measure of a subject's level of drowsiness. Respondents must choose statements that most accurately describe their level of sleepiness over the past 7 days. Scoring was based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). Higher scores denoted more drowsiness.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">403</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Pimavanserin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, taken as two tablets + background antipsychotic, once daily by mouth</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimavanserin</intervention_name>
    <description>Pimavanserin 34 mg, 20 mg, or 10 mg, taken as two tablets, once daily by mouth</description>
    <arm_group_label>Pimavanserin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, taken as two tablets, once daily by mouth</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients, between 18 and 55 years of age&#xD;
&#xD;
          2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year&#xD;
&#xD;
          3. Has predominant negative symptoms according to predefined study criteria&#xD;
&#xD;
          4. The main background antipsychotic with which the subject is being treated must be one&#xD;
             of the antipsychotics listed below:&#xD;
&#xD;
               -  Aripiprazole&#xD;
&#xD;
               -  Aripiprazole long-acting injectables:&#xD;
&#xD;
                    -  Abilify Maintena®&#xD;
&#xD;
                    -  Aristada®&#xD;
&#xD;
               -  Risperidone&#xD;
&#xD;
               -  Risperidone long-acting injection&#xD;
&#xD;
               -  Olanzapine&#xD;
&#xD;
               -  Lurasidone&#xD;
&#xD;
               -  Cariprazine&#xD;
&#xD;
               -  Brexpiprazole&#xD;
&#xD;
               -  Asenapine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has a psychiatric disorder other than schizophrenia&#xD;
&#xD;
          2. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested&#xD;
             prohibited substance of potential abuse, except marijuana&#xD;
&#xD;
             a. Patients with a result indicating the presence of marijuana are permitted if they&#xD;
             agree to abstain from marijuana use during the study and the medical monitor approves&#xD;
             the subject's participation&#xD;
&#xD;
          3. Patient has current evidence of a serious and/or unstable psychiatric, neurologic,&#xD;
             cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other&#xD;
             medical disorder, including cancer or malignancies, which would affect the patient's&#xD;
             ability to participate in the program&#xD;
&#xD;
          4. Patient has had a myocardial infarction in the last six months&#xD;
&#xD;
          5. Patient has a family or personal history or symptoms of long QT syndrome&#xD;
&#xD;
          6. Patient has been hospitalized due to inadequate family support or care at the&#xD;
             patient's primary residence, during the 8 weeks prior to screening&#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>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bellflower</city>
        <state>California</state>
        <zip>90706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lemon Grove</city>
        <state>California</state>
        <zip>91945</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Norwalk</city>
        <state>California</state>
        <zip>90650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lauderhill</city>
        <state>Florida</state>
        <zip>33319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Downingtown</city>
        <state>Pennsylvania</state>
        <zip>19335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Irving</city>
        <state>Texas</state>
        <zip>75062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richardson</city>
        <state>Texas</state>
        <zip>75080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sofia</city>
        <zip>1202</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sofia</city>
        <zip>1408</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sofia</city>
        <zip>1680</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Targovishte</city>
        <zip>7700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tserova Koria</city>
        <zip>5047</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Varna</city>
        <zip>9020</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Penticton</city>
        <state>British Columbia</state>
        <zip>V2A4M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chatham</city>
        <state>Ontario</state>
        <zip>N7L1C1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3QA 1A1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <zip>M6J 1H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hradec Králové</city>
        <state>Vekose</state>
        <zip>50341</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plzen</city>
        <zip>31200</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 10</city>
        <zip>10000</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 10</city>
        <zip>10600</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 6</city>
        <zip>16000</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Říčany</city>
        <zip>25101</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kalocsa</city>
        <state>Bács-Kiskun Megya</state>
        <zip>6300</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <state>Pest Megye</state>
        <zip>1036</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <state>Pest Megye</state>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <zip>1084</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <zip>1135</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gyula</city>
        <zip>5700</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pecs</city>
        <zip>7633</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Białystok</city>
        <zip>15-756</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-080</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lublin</city>
        <zip>20-080</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lublin</city>
        <zip>20-582</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pruszcz Gdański</city>
        <zip>83-000</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roshchino</city>
        <state>Leningrad Region</state>
        <zip>188820</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plekhanovo</city>
        <state>Lipetsk Region</state>
        <zip>399313</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ekaterinburg</city>
        <zip>620030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Petersburg</city>
        <zip>192019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Petersburg</city>
        <zip>193167</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Petersburg</city>
        <zip>195112</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Samara</city>
        <zip>443016</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Smolensk</city>
        <zip>214019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Stavropol</city>
        <zip>355000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Belgrade</city>
        <zip>11 000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kovin</city>
        <zip>26 220</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kovin</city>
        <zip>26220</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kragujevac</city>
        <zip>34 000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nis</city>
        <zip>18 000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08830</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oviedo</city>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valladolid</city>
        <zip>47016</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zamora</city>
        <zip>49021</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dnipro</city>
        <zip>49005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hlevakha</city>
        <zip>08631</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kherson</city>
        <zip>73488</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <zip>01133</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <zip>02192</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <zip>04080</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <zip>08631</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lviv</city>
        <zip>79017</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lviv</city>
        <zip>79021</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Odessa</city>
        <zip>65014</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oleksandrivka</city>
        <zip>67513</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poltava</city>
        <zip>36013</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Smila</city>
        <zip>20708</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vinnytsia</city>
        <zip>21005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <results_first_submitted>October 16, 2020</results_first_submitted>
  <results_first_submitted_qc>December 1, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 22, 2020</results_first_posted>
  <last_update_submitted>December 1, 2020</last_update_submitted>
  <last_update_submitted_qc>December 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</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>Schizophrenia</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>March 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT02970305/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>May 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT02970305/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pimavanserin</title>
          <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="201"/>
                <participants group_id="P2" count="202"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="172"/>
                <participants group_id="P2" count="174"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliance with study drug</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <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="12"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not further specified</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </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="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients randomised and treated with at least one dose of study medication</population>
      <group_list>
        <group group_id="B1">
          <title>Pimavanserin</title>
          <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</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="201"/>
            <count group_id="B2" value="202"/>
            <count group_id="B3" value="403"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.7" spread="9.37"/>
                    <measurement group_id="B2" value="36.7" spread="9.24"/>
                    <measurement group_id="B3" value="37.2" spread="9.31"/>
                  </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="70"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="135"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="131"/>
                    <measurement group_id="B2" value="137"/>
                    <measurement group_id="B3" value="268"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="187"/>
                    <measurement group_id="B2" value="186"/>
                    <measurement group_id="B3" value="373"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Schizophrenia diagnosis confirmed by SCID-5-CT</title>
          <description>SCID-5-CT: Structured Clinical Interview for DSM-5, Clinical Trials Version</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="201"/>
                    <measurement group_id="B2" value="202"/>
                    <measurement group_id="B3" value="403"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score</title>
        <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score</title>
          <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.8" spread="0.60"/>
                    <measurement group_id="O2" value="61.0" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.5" spread="0.69"/>
                    <measurement group_id="O2" value="-8.8" spread="0.69"/>
                  </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_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0434</p_value>
            <method>Mixed-effects model for repeated measure</method>
            <param_type>Difference in MMRM LSMs</param_type>
            <param_value>-1.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.95</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.8</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score</title>
        <description>The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on 4 main areas i.e. (a) socially useful activities, including work and study; (2) personal and social relationships, (3) self-care; and (4) disturbing and aggressive behaviors. The time period assessed is &quot;past month&quot;. Higher scores denote better psychosocial functioning</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score</title>
          <description>The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on 4 main areas i.e. (a) socially useful activities, including work and study; (2) personal and social relationships, (3) self-care; and (4) disturbing and aggressive behaviors. The time period assessed is &quot;past month&quot;. Higher scores denote better psychosocial functioning</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.2" spread="0.83"/>
                    <measurement group_id="O2" value="46.7" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="0.70"/>
                    <measurement group_id="O2" value="8.4" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26</title>
        <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.&#xD;
NSA-16 responders were defined as patients with at least 20, 30, 50, or 75% percentage improvement in NSA-16 total score from baseline.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score and had no missing values at Week 26.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26</title>
          <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.&#xD;
NSA-16 responders were defined as patients with at least 20, 30, 50, or 75% percentage improvement in NSA-16 total score from baseline.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score and had no missing values at Week 26.</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="174"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least 20% improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93"/>
                    <measurement group_id="O2" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 30% improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 50% improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 75% improvement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating</title>
        <description>The global negative symptoms rating of the NSA-16 assesses overall severity on a 7-point scale from 1 to 7, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating</title>
          <description>The global negative symptoms rating of the NSA-16 assesses overall severity on a 7-point scale from 1 to 7, with higher scores denoting more severe negative symptoms in schizophrenia.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="0.05"/>
                    <measurement group_id="O2" value="4.8" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="0.06"/>
                    <measurement group_id="O2" value="-0.7" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores</title>
        <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.</description>
        <time_frame>From baseline (BL) to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores</title>
          <description>The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Communication, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" spread="0.22"/>
                    <measurement group_id="O2" value="12.3" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Communication, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="0.21"/>
                    <measurement group_id="O2" value="-2.0" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotion/affect, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="198"/>
                    <count group_id="O2" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" spread="0.14"/>
                    <measurement group_id="O2" value="12.5" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotion/affect, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="171"/>
                    <count group_id="O2" value="172"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.17"/>
                    <measurement group_id="O2" value="-1.6" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Involvement, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="198"/>
                    <count group_id="O2" value="199"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" spread="0.16"/>
                    <measurement group_id="O2" value="12.6" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Involvement, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="172"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="0.17"/>
                    <measurement group_id="O2" value="-1.4" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Motivation, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="198"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.7" spread="0.18"/>
                    <measurement group_id="O2" value="16.6" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Motivation, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" spread="0.20"/>
                    <measurement group_id="O2" value="-2.2" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Retardation, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" spread="0.12"/>
                    <measurement group_id="O2" value="7.0" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Retardation, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="0.13"/>
                    <measurement group_id="O2" value="-1.5" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score</title>
        <description>The CGI-SCH-S is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score</title>
          <description>The CGI-SCH-S is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="0.04"/>
                    <measurement group_id="O2" value="4.7" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="0.06"/>
                    <measurement group_id="O2" value="-0.6" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26</title>
        <description>The CGI-SCH-I is a clinician-rated, 7-point scale to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The score could range from 1 (very much improved) to 7 (very much worse).</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26</title>
          <description>The CGI-SCH-I is a clinician-rated, 7-point scale to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The score could range from 1 (very much improved) to 7 (very much worse).</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="174"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="0.07"/>
                    <measurement group_id="O2" value="3.1" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases</title>
        <description>The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The 7-point scores range from 1 (very much improved) to 7 (very much worse); responders were defined as those with CGI-SCH-I of 1 or 2.&#xD;
The analysis includes observed cases; missing cases were not imputed.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug); had a baseline value and at least one post-baseline value for NSA-16 total score; and had no missing values at Week 26.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases</title>
          <description>The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The 7-point scores range from 1 (very much improved) to 7 (very much worse); responders were defined as those with CGI-SCH-I of 1 or 2.&#xD;
The analysis includes observed cases; missing cases were not imputed.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug); had a baseline value and at least one post-baseline value for NSA-16 total score; and had no missing values at Week 26.</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="174"/>
                <count group_id="O2" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score</title>
        <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score is the sum of scores and ranges from a minimum of 30 to a maximum of 210. Higher scores denote more severe symptoms.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score</title>
          <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score is the sum of scores and ranges from a minimum of 30 to a maximum of 210. Higher scores denote more severe symptoms.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.2" spread="0.70"/>
                    <measurement group_id="O2" value="79.4" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.7" spread="0.75"/>
                    <measurement group_id="O2" value="-8.6" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores</title>
        <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS has 3 subscales that are the sums of the respective item scores, including the positive scale (min 7, max 49), negative scale (min 7, max 49), and general psychopathology scale (min 16, max 112). Higher scores denote more severe symptoms.</description>
        <time_frame>From baseline (BL) to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores</title>
          <description>The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS has 3 subscales that are the sums of the respective item scores, including the positive scale (min 7, max 49), negative scale (min 7, max 49), and general psychopathology scale (min 16, max 112). Higher scores denote more severe symptoms.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Positive subscale, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" spread="0.24"/>
                    <measurement group_id="O2" value="13.7" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive subscale, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="0.19"/>
                    <measurement group_id="O2" value="-0.8" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative subscale, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.5" spread="0.26"/>
                    <measurement group_id="O2" value="27.5" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative subscale, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="0.29"/>
                    <measurement group_id="O2" value="-3.8" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General psychopathology subscale, BL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.6" spread="0.44"/>
                    <measurement group_id="O2" value="38.2" spread="0.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General psychopathology subscale, CFB to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.1" spread="0.43"/>
                    <measurement group_id="O2" value="-4.0" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score</title>
        <description>The BACS is a performance-based assessment of treatment-related changes in cognition, assessing 6 domains of verbal memory and learning; working memory; motor function; verbal fluency; attention and speed of processing; and executive function. The 6 domains with their raw scores are: verbal memory 0-75; digit sequencing 0-28; token motor 0-100; verbal fluency 0-225; symbol coding 0-110; Tower of London 0-22. For each domain, higher scores reflect better cognition. Raw scores are converted to age and sex-corrected normalized scores. The BACS composite score is calculated as the mean of the normalized scores from the 6 subscale scores, standardized so that the mean of the BACS composite score in the healthy normative sample is 50 and the standard deviation is 10.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score. Analysis only included patients with data/endpoint assessment and additionally excluded patients with raw scores outside of the score range.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score</title>
          <description>The BACS is a performance-based assessment of treatment-related changes in cognition, assessing 6 domains of verbal memory and learning; working memory; motor function; verbal fluency; attention and speed of processing; and executive function. The 6 domains with their raw scores are: verbal memory 0-75; digit sequencing 0-28; token motor 0-100; verbal fluency 0-225; symbol coding 0-110; Tower of London 0-22. For each domain, higher scores reflect better cognition. Raw scores are converted to age and sex-corrected normalized scores. The BACS composite score is calculated as the mean of the normalized scores from the 6 subscale scores, standardized so that the mean of the BACS composite score in the healthy normative sample is 50 and the standard deviation is 10.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score. Analysis only included patients with data/endpoint assessment and additionally excluded patients with raw scores outside of the score range.</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="197"/>
                <count group_id="O2" value="199"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="197"/>
                    <count group_id="O2" value="199"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.94" spread="1.271"/>
                    <measurement group_id="O2" value="20.99" spread="1.198"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="170"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.33" spread="0.719"/>
                    <measurement group_id="O2" value="4.16" spread="0.696"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score</title>
        <description>The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a subject who is fully adherent to the prescribed medication would answer as &quot;True&quot; and 4 items (2, 5, 6, and 8) that a subject who is fully adherent to the prescribed medication would answer as &quot;False.&quot; A correct answer is scored +1 and an incorrect answer is scored -1. The total score is the sum of pluses and minuses, which can range from -10 to 10 in increments of 2. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (non-adherent). Higher scores denote better adherence.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score</title>
          <description>The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a subject who is fully adherent to the prescribed medication would answer as &quot;True&quot; and 4 items (2, 5, 6, and 8) that a subject who is fully adherent to the prescribed medication would answer as &quot;False.&quot; A correct answer is scored +1 and an incorrect answer is scored -1. The total score is the sum of pluses and minuses, which can range from -10 to 10 in increments of 2. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (non-adherent). Higher scores denote better adherence.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="0.22"/>
                    <measurement group_id="O2" value="5.7" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.23"/>
                    <measurement group_id="O2" value="0.2" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score</title>
        <description>The KSS is a self-reported subjective measure of a subject's level of drowsiness. Respondents must choose statements that most accurately describe their level of sleepiness over the past 7 days. Scoring was based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). Higher scores denoted more drowsiness.</description>
        <time_frame>From baseline to Week 26</time_frame>
        <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimavanserin</title>
            <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score</title>
          <description>The KSS is a self-reported subjective measure of a subject's level of drowsiness. Respondents must choose statements that most accurately describe their level of sleepiness over the past 7 days. Scoring was based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). Higher scores denoted more drowsiness.</description>
          <population>Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.</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="199"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="201"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="0.11"/>
                    <measurement group_id="O2" value="4.8" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="173"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="0.12"/>
                    <measurement group_id="O2" value="-0.6" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26</time_frame>
      <desc>The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).</desc>
      <group_list>
        <group group_id="E1">
          <title>Pimavanserin</title>
          <description>Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).&#xD;
Patients were to continue their background antipsychotic treatment</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Pimavanserin matching placebo once daily&#xD;
Patients were to continue their background antipsychotic treatment</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</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="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="202"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="201"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.0</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="20" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="17" subjects_affected="13" subjects_at_risk="201"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="202"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="201"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="202"/>
              </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 his/her 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>
    <point_of_contact>
      <name_or_title>Sr. Dir. Medical Information and Medical Communications</name_or_title>
      <organization>ACADIA Pharmaceuticals Inc.</organization>
      <phone>+1-858-261 ext 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/NCT02970305
org study id: ACP-103-038
secondary id: 2016-003436-20
nct id: NCT02970305
lead sponsor: 
has dmc: Yes
To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive
      placebo in the treatment of the negative symptoms of schizophrenia
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score
time frame: From baseline to Week 26
description: The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
measure: Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score
time frame: From baseline to Week 26
description: The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on 4 main areas i.e. (a) socially useful activities, including work and study; (2) personal and social relationships, (3) self-care; and (4) disturbing and aggressive behaviors. The time period assessed is "past month". Higher scores denote better psychosocial functioning
measure: Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
time frame: From baseline to Week 26
description: The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
NSA-16 responders were defined as patients with at least 20, 30, 50, or 75% percentage improvement in NSA-16 total score from baseline.
measure: Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
time frame: From baseline to Week 26
description: The global negative symptoms rating of the NSA-16 assesses overall severity on a 7-point scale from 1 to 7, with higher scores denoting more severe negative symptoms in schizophrenia.
measure: Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
time frame: From baseline (BL) to Week 26
description: The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.
measure: Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score
time frame: From baseline to Week 26
description: The CGI-SCH-S is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).
measure: Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26
time frame: From baseline to Week 26
description: The CGI-SCH-I is a clinician-rated, 7-point scale to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The score could range from 1 (very much improved) to 7 (very much worse).
measure: Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases
time frame: From baseline to Week 26
description: The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The 7-point scores range from 1 (very much improved) to 7 (very much worse); responders were defined as those with CGI-SCH-I of 1 or 2.
The analysis includes observed cases; missing cases were not imputed.
measure: Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score
time frame: From baseline to Week 26
description: The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score is the sum of scores and ranges from a minimum of 30 to a maximum of 210. Higher scores denote more severe symptoms.
measure: Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
time frame: From baseline (BL) to Week 26
description: The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS has 3 subscales that are the sums of the respective item scores, including the positive scale (min 7, max 49), negative scale (min 7, max 49), and general psychopathology scale (min 16, max 112). Higher scores denote more severe symptoms.
measure: Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
time frame: From baseline to Week 26
description: The BACS is a performance-based assessment of treatment-related changes in cognition, assessing 6 domains of verbal memory and learning; working memory; motor function; verbal fluency; attention and speed of processing; and executive function. The 6 domains with their raw scores are: verbal memory 0-75; digit sequencing 0-28; token motor 0-100; verbal fluency 0-225; symbol coding 0-110; Tower of London 0-22. For each domain, higher scores reflect better cognition. Raw scores are converted to age and sex-corrected normalized scores. The BACS composite score is calculated as the mean of the normalized scores from the 6 subscale scores, standardized so that the mean of the BACS composite score in the healthy normative sample is 50 and the standard deviation is 10.
measure: Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score
time frame: From baseline to Week 26
description: The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a subject who is fully adherent to the prescribed medication would answer as "True" and 4 items (2, 5, 6, and 8) that a subject who is fully adherent to the prescribed medication would answer as "False." A correct answer is scored +1 and an incorrect answer is scored -1. The total score is the sum of pluses and minuses, which can range from -10 to 10 in increments of 2. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (non-adherent). Higher scores denote better adherence.
measure: Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score
time frame: From baseline to Week 26
description: The KSS is a self-reported subjective measure of a subject's level of drowsiness. Respondents must choose statements that most accurately describe their level of sleepiness over the past 7 days. Scoring was based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). Higher scores denoted more drowsiness.
arm group label: Pimavanserin
arm group type: Experimental
description: Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, taken as two tablets + background antipsychotic, once daily by mouth
intervention type: Drug
intervention name: Pimavanserin
description: Pimavanserin 34 mg, 20 mg, or 10 mg, taken as two tablets, once daily by mouth
arm group label: Pimavanserin
intervention type: Drug
intervention name: Placebo
description: Placebo, taken as two tablets, once daily by mouth
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
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country: Bulgaria
country: Canada
country: Czechia
country: Hungary
country: Poland
country: Russian Federation
country: Serbia
country: Spain
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Pimavanserin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 