<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03230864</url>
  </required_header>
  <id_info>
    <org_study_id>17303A</org_study_id>
    <nct_id>NCT03230864</nct_id>
  </id_info>
  <brief_title>Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia</brief_title>
  <acronym>Anew</acronym>
  <official_title>Interventional, Randomized, Double-blind, Active-controlled Study of the Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lundbeck A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>H. Lundbeck A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in&#xD;
      patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia&#xD;
      (TRS)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on&#xD;
      risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to&#xD;
      either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective&#xD;
      confirmation (PC) period.&#xD;
&#xD;
      The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks),&#xD;
      a Double-blind Treatment (DBT) Period (8 weeks), and a Safety Follow-up Period (6 weeks).&#xD;
&#xD;
      Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn&#xD;
      from the study after the PC period.&#xD;
&#xD;
      Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT&#xD;
      period and were randomized into one of the 2 treatmetn arms (1:1) with either Lu AF35700 10&#xD;
      mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the&#xD;
      dose set at the last visit of the PC period. This means that approximately half of the&#xD;
      confirmed treatment-resistant patients were randomised back to the failed treatment in the PC&#xD;
      period.&#xD;
&#xD;
      Data was not collected seperately for the DBT olanzapine and DBT risperidone participants,&#xD;
      and there was no intent to compare Lu AF35700 to each drug seperately.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    New data; the study was terminated based on new efficacy data from another study&#xD;
  </why_stopped>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Actual">February 5, 2019</completion_date>
  <primary_completion_date type="Actual">December 23, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score</measure>
    <time_frame>From Randomization to Week 8</time_frame>
    <description>PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score</measure>
    <time_frame>From Randomization to Week 8</time_frame>
    <description>CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score</measure>
    <time_frame>From Randomization to Week 8</time_frame>
    <description>The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Randomization to Week 8 in PANSS Marder Negative Factor Score</measure>
    <time_frame>From Randomization to Week 8</time_frame>
    <description>The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>at Week 8</time_frame>
    <description>Response is defined as a ≥20% reduction in PANSS total score from Randomization</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">119</enrollment>
  <condition>Treatment-resistant Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Prospective Confirmation (PC) Period</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double-blind treatment (DBT) period, Lu AF35700 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DBT Period, Continued treatment from PC Period</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lu AF35700</intervention_name>
    <description>10 mg/day, encapsulated tablets, orally</description>
    <arm_group_label>Double-blind treatment (DBT) period, Lu AF35700 10 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risperidone</intervention_name>
    <description>4-6 mg/day, encapsulated tablets, orally</description>
    <arm_group_label>DBT Period, Continued treatment from PC Period</arm_group_label>
    <arm_group_label>Prospective Confirmation (PC) Period</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olanzapine</intervention_name>
    <description>15-20 mg/day, encapsulated tablets, orally</description>
    <arm_group_label>DBT Period, Continued treatment from PC Period</arm_group_label>
    <arm_group_label>Prospective Confirmation (PC) Period</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient has schizophrenia, diagnosed according to DSM-5(TM). (Diagnostic and&#xD;
             Statistical Manual of Mental Disorders) and confirmed by the Mini International&#xD;
             Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI-Schz).&#xD;
&#xD;
          -  The patient is receiving treatment with a psychiatrist in either an inpatient or&#xD;
             outpatient facility.&#xD;
&#xD;
          -  The patient has been treated with adequate dose(s) of antipsychotic drug treatment for&#xD;
             at least 2 weeks prior to the Screening Visit.&#xD;
&#xD;
          -  The patient has failed to show an adequate response in the level of psychotic symptoms&#xD;
             during at least one documented treatment trial with an adequate dose of an&#xD;
             antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks)&#xD;
             within 2 years prior to the Screening Visit. The failure to respond to the current&#xD;
             antipsychotic drug treatment trial may be considered a retrospective failed treatment,&#xD;
             if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic&#xD;
             drug(s).&#xD;
&#xD;
          -  The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥&#xD;
             &quot;Moderate&quot; on 1-7 scale) on at least 2 of the following PANSS items at the Screening&#xD;
             and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory&#xD;
             behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the&#xD;
             patient has a CGI-S score of ≥4 (≥ &quot;Moderately ill&quot;) at the Screening and at Baseline&#xD;
             1 (Week 0) Visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient has any current primary psychiatric disorder other than schizophrenia, as&#xD;
             assessed using the MINI-Schz.&#xD;
&#xD;
          -  The patient suffers from mental retardation, organic mental disorders, or mental&#xD;
             disorders due to a general medical condition (DSM-5™ criteria).&#xD;
&#xD;
          -  The patient is experiencing an acute exacerbation of his/her psychotic symptoms.&#xD;
&#xD;
          -  The patient has been treated with, AND is resistant to, clozapine according to the&#xD;
             investigator's judgement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Email contact via H.Lundbeck A/S</last_name>
    <role>Study Director</role>
    <affiliation>LundbeckClinicalTrials@Lundbeck.com</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Diego Health System</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Cognitive Neurology Clinic &amp; ADRC</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corrigan Mental Health Center</name>
      <address>
        <city>Fall River</city>
        <state>Massachusetts</state>
        <zip>02720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Massachusetts Medical Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605-2610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Clinical Research Institute PC</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kalamazoo Community Mental Health and Substance Abuse Services</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PsychCare Consultants Research</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Creighton University</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychiatric and Behavioral Solutions</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPH - Kardzhali</name>
      <address>
        <city>Kardzhali</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatric Hospital</name>
      <address>
        <city>Novi Iskar</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT</name>
      <address>
        <city>Pleven</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatric Hospital</name>
      <address>
        <city>Radnevo</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DCC St. Vrach and St.St. Kuzma and Damian</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHC - Sofia</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT - Targovishte</name>
      <address>
        <city>Tărgovište</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Takeda General Hospital - JP0009</name>
      <address>
        <city>Aizu-Wakamatsu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Takeda General Hospital</name>
      <address>
        <city>Fukushima</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kohnodai Hospital</name>
      <address>
        <city>Ichikawa</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nara Medical University Hospital</name>
      <address>
        <city>Kashihara</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Occupational and Environmental Health Hospital</name>
      <address>
        <city>Kitakyushu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sankeikai Nishigahara Hospital - JP0008</name>
      <address>
        <city>Kita</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Center of Neurology and Psychiatry</name>
      <address>
        <city>Kodaira</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Satokai Yuge Hospital</name>
      <address>
        <city>Kumamoto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHO Ryukyu Hospital</name>
      <address>
        <city>Kunigami</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fujita Health University Hospital</name>
      <address>
        <city>Toyoake</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sverdlovsk Regional Clinical Psychiatric Hospital</name>
      <address>
        <city>Ekaterinburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GUZ Lipetsk Regional psychoneurological Hospital 1</name>
      <address>
        <city>Lipetsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lipetsk Regional Psychoneurological Hospital</name>
      <address>
        <city>Lipetsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Psychiatric Hospital # 6</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychoneurological Dispensary #10</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychoneurological Dispensary #1</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samara Psychiatric Hospital</name>
      <address>
        <city>Samara</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tomsk National Research Medical Centre of the Russian Academy of Sciences</name>
      <address>
        <city>Tomsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yaroslavl Regional Clinical Psychiatric Hospital</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Edinburgh Hospital</name>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Maudsley Hospital - GB0001</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Maudsley Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester Mental Health &amp; Social Care NHS Trust - GB0003</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester Mental Health &amp; Social Care NHS Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Japan</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <results_first_submitted>December 20, 2019</results_first_submitted>
  <results_first_submitted_qc>December 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 7, 2020</results_first_posted>
  <last_update_submitted>January 10, 2020</last_update_submitted>
  <last_update_submitted_qc>January 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Treatment-resistant schizophrenia</keyword>
  <keyword>Lu AF35700</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Schizophrenia, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olanzapine</mesh_term>
    <mesh_term>Risperidone</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>September 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03230864/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>March 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03230864/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Patients who did not fulfil the randomization criteria for the DBT period, were withdrawn from the study after the PC period. Patients who fulfilled the randomization crietria for the DBT period, continued into the DBT period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Prospective Confirmation (PC) Period, Risperidone</title>
          <description>Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks&#xD;
Risperidone: 4-6 mg/day, encapsulated tablets, orally</description>
        </group>
        <group group_id="P2">
          <title>PC Period, Olanzapine</title>
          <description>Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks&#xD;
Olanzapine: 15-20 mg/day, encapsulated tablets, orally</description>
        </group>
        <group group_id="P3">
          <title>Double-blind (DBT), Lu AF35700 10 mg</title>
          <description>Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks</description>
        </group>
        <group group_id="P4">
          <title>DBT, Continued Treatment From PC Period</title>
          <description>Patients in this arm will continue the treatment allocated in the PC period at the dose set at the last visit of the PC period. The analysis is made independent on which treatment the patient was done (risperidone or olanzapine). 8 weeks treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Prospective Confirmation (PC) Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
                <participants group_id="P2" count="51"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not fulfill rand criteria DBT</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Personnel Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Double Blind Treatment (DBT) Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="27"/>
                <participants group_id="P4" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Non-randomized Patients</title>
          <description>Patients not randomized to double-blind treatment period, i.e. withdrawn from the study during or after the PC period, were analyzed as one arm, independent of treatment</description>
        </group>
        <group group_id="B2">
          <title>Double-blind Treatment (DBT) Period, Lu AF35700 10 mg</title>
          <description>Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks</description>
        </group>
        <group group_id="B3">
          <title>DBT, Continued Treatment From PC Period</title>
          <description>Patients in this arm continued with the same treatment and dose as at the last visit of the PC period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm independent of treatment.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="51"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="33"/>
            <count group_id="B4" value="119"/>
          </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="42.6" spread="12.53"/>
                    <measurement group_id="B2" value="42.9" spread="11.26"/>
                    <measurement group_id="B3" value="42" spread="12.26"/>
                    <measurement group_id="B4" value="42.5" spread="12"/>
                  </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="23"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="112"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>PANSS total score</title>
          <description>Positive and Negative Syndrome Scale (PANNS) total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symprom not present) to 7 (symptom extremely severe). PANNS total score was calculated as sum of all items on the scale and ranged from 30 to 210. A higher score corresponded to a worse severity of schizophrenia.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="98.1" spread="10.78"/>
                    <measurement group_id="B2" value="102.3" spread="12"/>
                    <measurement group_id="B3" value="101.6" spread="11.95"/>
                    <measurement group_id="B4" value="100.3" spread="11.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CGI-S score</title>
          <description>CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.8" spread="0.64"/>
                    <measurement group_id="B2" value="4.8" spread="0.57"/>
                    <measurement group_id="B3" value="4.9" spread="0.55"/>
                    <measurement group_id="B4" value="4.82" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score</title>
        <description>PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.</description>
        <time_frame>From Randomization to Week 8</time_frame>
        <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the full-analysis set (FAS) with a week 8 observation</population>
        <group_list>
          <group group_id="O1">
            <title>Double-blind Treatment (DBT) Period, Lu AF35700 10 mg</title>
            <description>Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>DBT, Continued Treatment From PC Period</title>
            <description>Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score</title>
          <description>PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.</description>
          <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the full-analysis set (FAS) with a week 8 observation</population>
          <units>units 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="27"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.71" spread="2.22"/>
                    <measurement group_id="O2" value="-10.19" spread="2.16"/>
                  </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>
            <groups_desc>The mean changes from randomization in PANNS total score was analysed using a mixed model for repeated measures (MMRM) approach. The model will include the fixed, categorical effects of treatment, strata, visit, treatment-by-visit interaction, fixed covariates of baseline scores and baseline scores-by-visit interaction. An unstructured (co)variance structure will be used to model the within-patient errors. The Kenward-Roger approximation will be used to estimate denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0809</p_value>
            <method>Mixed Model Repeated Measures</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>5.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.70</ci_lower_limit>
            <ci_upper_limit>11.65</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score</title>
        <description>CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening</description>
        <time_frame>From Randomization to Week 8</time_frame>
        <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
        <group_list>
          <group group_id="O1">
            <title>DBT, Lu AF35700 10 mg</title>
            <description>10 mg encapsulated tablets administered orally, once daily.&#xD;
Lu AF35700: 10 mg/day, encapsulated tablets, orally</description>
          </group>
          <group group_id="O2">
            <title>DBT, Continued Treatment</title>
            <description>Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score</title>
          <description>CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening</description>
          <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
          <units>units 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="27"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.18" spread="0.12"/>
                    <measurement group_id="O2" value="-0.37" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score</title>
        <description>The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.</description>
        <time_frame>From Randomization to Week 8</time_frame>
        <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
        <group_list>
          <group group_id="O1">
            <title>DBT, Lu AF35700 10 mg</title>
            <description>10 mg encapsulated tablets administered orally, once daily.&#xD;
Lu AF35700: 10 mg/day, encapsulated tablets, orally</description>
          </group>
          <group group_id="O2">
            <title>DBT, Continued Treatment</title>
            <description>Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score</title>
          <description>The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.</description>
          <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
          <units>units 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="27"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.99" spread="1.64"/>
                    <measurement group_id="O2" value="-3.14" spread="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Randomization to Week 8 in PANSS Marder Negative Factor Score</title>
        <description>The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.</description>
        <time_frame>From Randomization to Week 8</time_frame>
        <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
        <group_list>
          <group group_id="O1">
            <title>DBT, Lu AF35700 10 mg</title>
            <description>10 mg encapsulated tablets administered orally, once daily.&#xD;
Lu AF35700: 10 mg/day, encapsulated tablets, orally</description>
          </group>
          <group group_id="O2">
            <title>DBT, Continued Treatment</title>
            <description>Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Randomization to Week 8 in PANSS Marder Negative Factor Score</title>
          <description>The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.</description>
          <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
          <units>units 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="27"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.51" spread="0.77"/>
                    <measurement group_id="O2" value="-1.74" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response</title>
        <description>Response is defined as a ≥20% reduction in PANSS total score from Randomization</description>
        <time_frame>at Week 8</time_frame>
        <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</population>
        <group_list>
          <group group_id="O1">
            <title>DBT, Lu AF35700 10 mg</title>
            <description>10 mg encapsulated tablets administered orally, once daily.&#xD;
Lu AF35700: 10 mg/day, encapsulated tablets, orally</description>
          </group>
          <group group_id="O2">
            <title>DBT, Continued Treatment</title>
            <description>Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)</description>
          </group>
        </group_list>
        <measure>
          <title>Response</title>
          <description>Response is defined as a ≥20% reduction in PANSS total score from Randomization</description>
          <population>Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation</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="27"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>20 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Prospective Confirmation (PC) Period - Risperidone</title>
          <description>Patients not randomized to double-blind treatment</description>
        </group>
        <group group_id="E2">
          <title>PC Period - Olanzapine</title>
          <description>Patients not randomized to double-blind treatment</description>
        </group>
        <group group_id="E3">
          <title>Double Blind Treatment (DBT) Period - Lu AF35700 10 mg</title>
          <description>Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks</description>
        </group>
        <group group_id="E4">
          <title>DBT Period, Continued Treatment From PC Period</title>
          <description>Patients in this arm continued with the same treatment and dose as at the last visit of the PC Period. This arm is analyzed as one single treatment arm independent on which treatment was administered (olanzapine or risperidone for 8 weeks).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA - 21.0</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="68"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA - 21.0</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="16" subjects_at_risk="68"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="35"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="35"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="68"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated early and hence the statistical analysis was conducted on a smaller sample size than originally planned.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Email contact via</name_or_title>
      <organization>H. Lundbeck A/S</organization>
      <phone>+4536301311</phone>
      <email>LundbeckClinicalTrials@Lundbeck.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/NCT03230864
org study id: 17303A
nct id: NCT03230864
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in
      patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia
      (TRS)
In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on
      risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to
      either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective
      confirmation (PC) period.

      The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks),
      a Double-blind Treatment (DBT) Period (8 weeks), and a Safety Follow-up Period (6 weeks).

      Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn
      from the study after the PC period.

      Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT
      period and were randomized into one of the 2 treatmetn arms (1:1) with either Lu AF35700 10
      mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the
      dose set at the last visit of the PC period. This means that approximately half of the
      confirmed treatment-resistant patients were randomised back to the failed treatment in the PC
      period.

      Data was not collected seperately for the DBT olanzapine and DBT risperidone participants,
      and there was no intent to compare Lu AF35700 to each drug seperately.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
time frame: From Randomization to Week 8
description: PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.
measure: Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
time frame: From Randomization to Week 8
description: CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening
measure: Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
time frame: From Randomization to Week 8
description: The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.
measure: Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
time frame: From Randomization to Week 8
description: The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.
measure: Response
time frame: at Week 8
description: Response is defined as a ≥20% reduction in PANSS total score from Randomization
arm group label: Prospective Confirmation (PC) Period
arm group type: Experimental
description: Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks
arm group label: Double-blind treatment (DBT) period, Lu AF35700 10 mg
arm group type: Experimental
description: Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks
arm group label: DBT Period, Continued treatment from PC Period
arm group type: Experimental
description: Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period
intervention type: Drug
intervention name: Lu AF35700
description: 10 mg/day, encapsulated tablets, orally
arm group label: Double-blind treatment (DBT) period, Lu AF35700 10 mg
intervention type: Drug
intervention name: Risperidone
description: 4-6 mg/day, encapsulated tablets, orally
arm group label: DBT Period, Continued treatment from PC Period
arm group label: Prospective Confirmation (PC) Period
intervention type: Drug
intervention name: Olanzapine
description: 15-20 mg/day, encapsulated tablets, orally
arm group label: DBT Period, Continued treatment from PC Period
arm group label: Prospective Confirmation (PC) Period
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Email contact via H.Lundbeck A/S
role: Study Director
affiliation: LundbeckClinicalTrials@Lundbeck.com
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country: Bulgaria
country: Japan
country: Russian Federation
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Schizophrenia, Treatment-Resistant
mesh term: Olanzapine
mesh term: Risperidone
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated early and hence the statistical analysis was conducted on a smaller sample size than originally planned.
point of contact: 