<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/NCT02978599</url>
  </required_header>
  <id_info>
    <org_study_id>7370</org_study_id>
    <secondary_id>U01MH094247-01</secondary_id>
    <nct_id>NCT02978599</nct_id>
  </id_info>
  <brief_title>Clinical Trial of AVL-3288 in Schizophrenia Patients</brief_title>
  <official_title>Double Blind, Two Dose, Cross-over Clinical Trial of the Positive Allosteric Modulator at the alpha7 Nicotinic Cholinergic Receptor AVL-3288 in Schizophrenia Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase,&#xD;
      cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of&#xD;
      AVL-3288 each compared to placebo, in patients with schizophrenia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be in 24 non-smoking outpatients with schizophrenia or schizoaffective&#xD;
      disorder. Subjects will complete three treatment phases, each involving 5 straight days of&#xD;
      taking AVL-3288 (10 mg or 30 mg study drug or placebo) followed by a 16 day washout period in&#xD;
      which subjects do not take the study drug to ensure that the drug is completed eliminated&#xD;
      from the body before the next phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">November 2, 2018</completion_date>
  <primary_completion_date type="Actual">October 26, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare effect of active drug (AVL-3288) to placebo on RBANS total score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RBANS index T-score subscales</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare effect of active drug (AVL-3288) to placebo on RBANS index T-score subscales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Psychiatric Rating Scale (BPRS) Total score</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare effect of active drug (AVL-3288) to placebo on BPRS Total Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calgary Depression Rating Scale (CDRS) Total score</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare effect of active drug (AVL-3288) to placebo on CDRS Total Score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Scale for the Assessment of Negative Symptoms (SANS) Total score</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare effect of active drug (AVL-3288) to placebo on SANS Total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P50 suppression measured by electroencephalographic (EEG)</measure>
    <time_frame>End of each 5-day treatment phase</time_frame>
    <description>Compare P50 suppression measured by EEG between active drug (AVL-3288) and placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensity of hippocampal BOLD fMRI signal during MRI scan</measure>
    <time_frame>end of each 5-day treatment phase</time_frame>
    <description>Compare intensity of Hippocampal BOLD signal between active drug (AVL-3288) and placebo</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <arm_group>
    <arm_group_label>AVL-3288 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AVL-3288 10 mg daily for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVL-3288 30 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AVL-3288 30 mg daily for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo daily for 5 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AVL-3288</intervention_name>
    <description>daily for 5 days</description>
    <arm_group_label>AVL-3288 10 mg</arm_group_label>
    <arm_group_label>AVL-3288 30 mg</arm_group_label>
    <other_name>Anvylic-3288</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>daily for 5 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  DSM-V diagnosis of schizophrenia or schizoaffective disorder&#xD;
&#xD;
          -  RBANS Total Scale Score &gt;62&#xD;
&#xD;
          -  Willing to provide informed consent&#xD;
&#xD;
          -  Medically stable for study participation&#xD;
&#xD;
          -  Taking an antipsychotic medication other than clozapine at a stable dose for at least&#xD;
             4 weeks&#xD;
&#xD;
          -  Judged clinically not to be at significant suicide or violence risk&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Substance abuse (excluding nicotine) within last 90 days&#xD;
&#xD;
          -  ECG abnormality that is clinically significant&#xD;
&#xD;
          -  Current clozapine use&#xD;
&#xD;
          -  Participation in a study of investigational medication/device within 4 weeks&#xD;
&#xD;
          -  Pregnancy, lactation, or lack of use of effective birth control&#xD;
&#xD;
          -  Active tobacco use&#xD;
&#xD;
          -  Presence or positive history of significant medical or neurological illness, including&#xD;
             cardiac illness, WBC &lt;3500/mm3, absolute neutrophil count &lt;1500/mm3, ALT or AST values&#xD;
             &gt;1.5 times upper limit of normal. Hemoglobin less than 130 g/L (13 g/dL) in males or&#xD;
             120 g/L (12 g/dL) in females or known HIV +&#xD;
&#xD;
          -  Contraindication to MRI scanning, including metal implants or claustrophobia&#xD;
&#xD;
          -  Medicinal patch, unless removed&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey A Lieberman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Joshua Kantrowitz</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02978599
org study id: 7370
secondary id: U01MH094247-01
nct id: NCT02978599
lead sponsor: 
collaborator: 
has dmc: Yes
Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase,
      cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of
      AVL-3288 each compared to placebo, in patients with schizophrenia.
This study will be in 24 non-smoking outpatients with schizophrenia or schizoaffective
      disorder. Subjects will complete three treatment phases, each involving 5 straight days of
      taking AVL-3288 (10 mg or 30 mg study drug or placebo) followed by a 16 day washout period in
      which subjects do not take the study drug to ensure that the drug is completed eliminated
      from the body before the next phase.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score
time frame: End of each 5-day treatment phase
description: Compare effect of active drug (AVL-3288) to placebo on RBANS total score
measure: RBANS index T-score subscales
time frame: End of each 5-day treatment phase
description: Compare effect of active drug (AVL-3288) to placebo on RBANS index T-score subscales
measure: Brief Psychiatric Rating Scale (BPRS) Total score
time frame: End of each 5-day treatment phase
description: Compare effect of active drug (AVL-3288) to placebo on BPRS Total Score.
measure: Calgary Depression Rating Scale (CDRS) Total score
time frame: End of each 5-day treatment phase
description: Compare effect of active drug (AVL-3288) to placebo on CDRS Total Score.
measure: Scale for the Assessment of Negative Symptoms (SANS) Total score
time frame: End of each 5-day treatment phase
description: Compare effect of active drug (AVL-3288) to placebo on SANS Total score
measure: P50 suppression measured by electroencephalographic (EEG)
time frame: End of each 5-day treatment phase
description: Compare P50 suppression measured by EEG between active drug (AVL-3288) and placebo
measure: Intensity of hippocampal BOLD fMRI signal during MRI scan
time frame: end of each 5-day treatment phase
description: Compare intensity of Hippocampal BOLD signal between active drug (AVL-3288) and placebo
arm group label: AVL-3288 10 mg
arm group type: Experimental
description: AVL-3288 10 mg daily for 5 days
arm group label: AVL-3288 30 mg
arm group type: Experimental
description: AVL-3288 30 mg daily for 5 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo daily for 5 days
intervention type: Drug
intervention name: AVL-3288
description: daily for 5 days
arm group label: AVL-3288 10 mg
arm group label: AVL-3288 30 mg
other name: Anvylic-3288
intervention type: Drug
intervention name: Placebo
description: daily for 5 days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Jeffrey A Lieberman, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Joshua Kantrowitz
investigator title: Assistant Professor of Clinical Psychiatry
mesh term: Schizophrenia
mesh term: Psychotic Disorders
sharing ipd: Yes