<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/NCT02218736</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00052485</org_study_id>
    <secondary_id>HHSN271201200006I</secondary_id>
    <nct_id>NCT02218736</nct_id>
  </id_info>
  <brief_title>Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a</brief_title>
  <acronym>FASTMAS_Kor2</acronym>
  <official_title>A Phase 2a Study to Evaluate the Kappa Opioid Receptor As a Target for the Treatment of Mood and Anxiety Spectrum Disorders by Evaluation of Whether CERC-501 Engages Key Neural Circuitry Related to the Hedonic Response</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Case Western Reserve University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The available treatment for patients with mood and anxiety disorders have significant&#xD;
      limitations (Rush, 2007; Denys and de Geus, 2005). There is a need to develop new treatments&#xD;
      for people with these disorders. Many research studies carried out in animals and a few&#xD;
      preliminary studies carried out in humans suggest that medications which block kappa opioid&#xD;
      receptors (KOR) have potential for being effective new treatments for patients with mood and&#xD;
      anxiety spectrum disorders. These medications have shown particular promise for improving one&#xD;
      important type of difficulty experienced by many patients who suffer from mood and anxiety&#xD;
      spectrum disorders referred to as anhedonia, which is an impairment in reward-related&#xD;
      function. In this study we will test the hypothesis that KOR antagonism is a promising means&#xD;
      of improving anhedonia in patients with mood and anxiety spectrum disorders. We will do so by&#xD;
      evaluating whether we can establish Proof of Concept (POC) that a relatively selective KOR&#xD;
      antagonist, CERC-501 (formerly known as LY2456302), engages neural circuits involved in&#xD;
      mediating reward-related function in patients with mood and anxiety spectrum disorders with&#xD;
      anhedonia. We are attempting to establish POC in this study in order to determine whether&#xD;
      there is a sufficient basis for pursuing future work evaluating whether KOR antagonism has&#xD;
      therapeutic effects on clinical and behavioral measures of reward-related functioning.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      FAST-MAS addresses an important problem and critical barrier to progress in Mood and Anxiety&#xD;
      Spectrum Disorders and if the aims of the project are achieved, FAST-MAS could shift&#xD;
      scientific knowledge, technical capacity, and clinical practice in a positive direction.&#xD;
&#xD;
      The Mood and Anxiety Spectrum disorders are both extremely common and associated with&#xD;
      significant morbidity and mortality and, as such, represent an important public health&#xD;
      problem in the United States.&#xD;
&#xD;
      The mood disorders include the following diagnostic entities: major depressive disorder&#xD;
      (MDD), bipolar disorder (including subtypes of mania, mixed state, and depressed, as well as&#xD;
      types I and II), and dysthymic disorder. Available epidemiologic data suggest that the&#xD;
      prevalence of these mood disorders is extremely high among adults in the United States,&#xD;
      approaching 10%. Among the mood disorders, MDD has high lifetime prevalence, with recent&#xD;
      estimates up to 16%. According to the World Health Organization (WHO), MDD is currently the&#xD;
      leading cause of disability with the greatest burden of illness in developed countries and&#xD;
      the third most common cause of disability worldwide. MDD is life shortening due to both&#xD;
      suicide and its association with increased mortality from other medical conditions. It is&#xD;
      also a highly recurrent condition with between 50% and 75% of persons diagnosed with MDD&#xD;
      experiencing more than one episode. Bipolar Disorder is also a highly recurrent condition.&#xD;
      The lifetime prevalence of bipolar disorder has been estimated to be approximately 3.4% in&#xD;
      the World Health Survey Initiative. Approximately 60% of affected individuals experience&#xD;
      severe or very severe role impairment based on the Sheehan Disability Scale and, like MDD,&#xD;
      bipolar disorder is associated with significant suicide risk.&#xD;
&#xD;
      The anxiety disorders are also very common and associated with significant adverse impact on&#xD;
      affected individuals and society. These disorders include the following diagnostic entities:&#xD;
      generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder, social&#xD;
      phobia, specific phobias, and post-traumatic stress disorder (PTSD). As a group, these&#xD;
      conditions affect approximately 18% of adults in a given year and they are associated with&#xD;
      significant co-morbidities and adverse consequences. Of the anxiety disorders, GAD appears to&#xD;
      be associated with the greatest per patient cost and disability with a degree of disability&#xD;
      comparable to that of MDD and comparable to chronic medical conditions such as arthritis,&#xD;
      diabetes, and peptic ulcer disease. It affects approximately 6.8 million adults in the U.S.&#xD;
      and is a highly chronic condition. Panic disorder affects about 6 million American adults and&#xD;
      is twice as common in women as men. Panic disorder is also highly disabling and often chronic&#xD;
      and even mild forms of this disorder are linked to significantly increased impairment in&#xD;
      function and quality of life as well as a number of comorbidities. Approximately 2.2 million&#xD;
      adults in the U.S. are affected by obsessive-compulsive disorder and this disorder is often&#xD;
      accompanied by psychiatric comorbidities. Roughly half of individuals with this condition&#xD;
      have a chronic unremitting course which is associated with significant disability and&#xD;
      morbidity. Social phobia, also known as social anxiety disorder, is seen in roughly 15&#xD;
      million adults in the U.S. and is often associated with MDD or other anxiety disorders. It is&#xD;
      generally a chronic condition that leads to a great degree of disability due to substantial&#xD;
      impairment in social, educational, and occupational function. Approximately 8 million adults&#xD;
      in the U.S. experience PTSD and approximately 12% of the population have PTSD at some point&#xD;
      in their lives and affected individuals frequently experience associated MDD, other anxiety&#xD;
      disorders and substance use problems. The level of disability associated with this condition&#xD;
      tends to be quite high and includes impairment in social and occupational function and&#xD;
      quality of life. There are also substantial financial and social costs associated with PTSD&#xD;
      due to increased hospitalization rates, suicidality, and substance use problem.&#xD;
&#xD;
      Mood disorders and anxiety disorders are highly prevalent conditions, many of which are&#xD;
      chronic, nearly all of which are associated with substantial comorbidities, disability and&#xD;
      impairment and some are associated with an increased risk for mortality. Despite the&#xD;
      availability of many pharmacologic, psychotherapeutic, brain stimulation, and combination&#xD;
      treatment options available to clinicians, many patients with Mood and Anxiety Spectrum&#xD;
      Disorders respond poorly to treatment. In light of the impairments, costs, and risks of these&#xD;
      disorders, the limitations of the available treatments represents an enormous burden to&#xD;
      public health and speak strongly to the need for new treatments for these conditions as well&#xD;
      as novel methodologies of treatment development that are not only faster than existing&#xD;
      methodologies but which also promote new ways of thinking about these disorders and their&#xD;
      treatment and capitalize on recent and ongoing developments in basic science.&#xD;
&#xD;
      This study will be a six-site randomized, double-blind, PBO (placebo) -controlled,&#xD;
      parallel-group mono-therapy study to assess the effects of CERC-501 (formerly known as&#xD;
      LY2456302) compared to PBO in adults age 21-65 years with mood and anxiety spectrum&#xD;
      disorders. We will recruit a total of 90 subjects, of which 45 will be randomized to CERC-501&#xD;
      and 45 to placebo for 8 weeks of treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2015</start_date>
  <completion_date type="Actual">December 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 2017</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>Health Services Research</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI</measure>
    <time_frame>baseline, Week 8</time_frame>
    <description>Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)</measure>
    <time_frame>8 weeks</time_frame>
    <description>To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). A single value was calculated for the average over 8 weeks. The SHAPS is a well-validated 14-item questionnaire used to assess anhedonia. It asks participants to agree or disagree with statements of hedonic response in pleasurable situations. Four responses are possible: Strongly disagree, Disagree, Agree, or Strongly agree. Each item is worded so that higher scores indicate greater pleasure capacity. A total score is derived by summing the responses to each item. Items answered &quot;strongly agree&quot; are coded as &quot;1&quot;, while &quot;strongly disagree&quot; are coded a score of &quot;4.&quot; Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task</measure>
    <time_frame>baseline, Week 8</time_frame>
    <description>To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function (level of reward learning). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">163</enrollment>
  <condition>ANXIETY DISORDERS (or Anxiety and Phobic Neuroses)</condition>
  <arm_group>
    <arm_group_label>CERC-501</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral daily administration of 10 mg placebo for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CERC-501</intervention_name>
    <description>Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
    <arm_group_label>CERC-501</arm_group_label>
    <other_name>Kappa Opioid Receptor Antagonist; LY2456302</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>oral dosing of 10 mg placebo daily for 8 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 21 and 65 years of age&#xD;
&#xD;
          -  Must meet DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders, 4th&#xD;
             edition, text revision) diagnostic criteria for: Major Depressive Disorder, Bipolar I&#xD;
             or II Depressed, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, or Post&#xD;
             Traumatic Stress Disorder&#xD;
&#xD;
          -  Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20&#xD;
&#xD;
          -  Reliable and willing to be available for the duration of the study&#xD;
&#xD;
          -  Willing and able to give written informed consent to participate&#xD;
&#xD;
          -  Able to understand and comply with instructions&#xD;
&#xD;
          -  If female of childbearing potential, must agree to use dual methods of contraception&#xD;
             and be willing and able to continue contraception for 6 weeks after the last dose of&#xD;
             study drug. Females using oral contraception must have started using it at least 2&#xD;
             months prior to the Baseline Visit&#xD;
&#xD;
          -  If male of childbearing potential, must have undergone surgical sterilization (such as&#xD;
             a vasectomy) or agree to use a condom used with a spermicide during participation in&#xD;
             the study and for 1 month afterward&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Expected to require hospitalization during the course of the study&#xD;
&#xD;
          -  Current/history of a psychotic disorder, current manic or mixed episode, autism&#xD;
             spectrum disorders, mental retardation&#xD;
&#xD;
          -  Met DSMIV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text&#xD;
             revision) criteria for substance abuse within the last 3 months or substance&#xD;
             dependence within the last 6 months, excluding caffeine and/or nicotine&#xD;
&#xD;
          -  History of unstable or untreated serious medical condition based on physician&#xD;
             evaluation, medical history, and screening laboratory testing&#xD;
&#xD;
          -  Active suicidal intent or plan, or history of attempt within the past 3 months based&#xD;
             on physician evaluation and Columbia Suicide Severity Rating Scale (C-SSRS)&#xD;
&#xD;
          -  Use of any antidepressant, antipsychotic, anxiolytic, anticonvulsant, mood&#xD;
             stabilizing, muscle relaxant, centrally acting antihistaminergic, stimulant or&#xD;
             insomnia medications (See Appendix 2) within 5 half-lives of baseline or at any time&#xD;
             during after baseline&#xD;
&#xD;
          -  Use of any medication that is primarily metabolized by Cytochrome P450 2C8 within 14&#xD;
             days of baseline or at any time during the study. This includes: Cerivastatin,&#xD;
             Paclitaxel, Repaglinide, Sorafenib, Rosiglitazone, Trimethoprim, Amodiaquine,&#xD;
             Morphine, Amiodarone, Cabazitaxel, Carbamazepine, Chloroquine, Ibuprofen, Trepostinil,&#xD;
             Torsemide.&#xD;
&#xD;
          -  Any contraindications to the magnetic resonance imaging procedures&#xD;
&#xD;
          -  Positive urine drug screen at any time during the study&#xD;
&#xD;
          -  Use of any investigational medication within 3 months prior to the start of this study&#xD;
             or scheduled to receive an investigational drug other than the study drug during the&#xD;
             course of this study&#xD;
&#xD;
          -  Known hypersensitivity to CERC-501 (formerly known as LY2456302)&#xD;
&#xD;
          -  History of severe allergies or multiple adverse drug reactions&#xD;
&#xD;
          -  History of gastric disease (including peptic ulcer disease, gastritis, upper GI&#xD;
             bleeding, or any GI precancerous condition), current clinically evident&#xD;
             gastrointestinal complaints, or positive urea breath test&#xD;
&#xD;
          -  Current use of a proton pump inhibitor or histamine 2 blocker, or a history of chronic&#xD;
             NSAID (nonsteroidal anti-inflammatory drug) use.&#xD;
&#xD;
          -  History of use of Salvia divinorum or use of Salvia divinorum at any time during the&#xD;
             study.&#xD;
&#xD;
          -  Any other condition that in the opinion of the investigator would preclude&#xD;
             participation in the study&#xD;
&#xD;
          -  Any smoking of cigarettes or use of other nicotine containing products within the last&#xD;
             month or at any time during the study&#xD;
&#xD;
          -  Pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard D Weiner, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Andrew Goddard, MD</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202-l7176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CaseWestern Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>70030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rorick-Kehn LM, Witkin JM, Statnick MA, Eberle EL, McKinzie JH, Kahl SD, Forster BM, Wong CJ, Li X, Crile RS, Shaw DB, Sahr AE, Adams BL, Quimby SJ, Diaz N, Jimenez A, Pedregal C, Mitch CH, Knopp KL, Anderson WH, Cramer JW, McKinzie DL. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014 Feb;77:131-44. doi: 10.1016/j.neuropharm.2013.09.021. Epub 2013 Sep 23.</citation>
    <PMID>24071566</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>November 1, 2018</results_first_submitted>
  <results_first_submitted_qc>December 14, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">January 8, 2019</results_first_posted>
  <last_update_submitted>December 14, 2018</last_update_submitted>
  <last_update_submitted_qc>December 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anhedonia</keyword>
  <keyword>Mood and Anxiety Spectrum Disorders</keyword>
  <keyword>CERC-501 (investigational product)</keyword>
  <keyword>Kappa Opioid Receptor (KOR)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Phobic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aticaprant</mesh_term>
    <mesh_term>Narcotic Antagonists</mesh_term>
  </intervention_browse>
  <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>October 6, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02218736/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>December 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02218736/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>69 participants screen failed, 2 were unable to complete baseline per protocol, 3 withdrew consent prior to baseline.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>CERC-501</title>
          <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
              </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="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who were randomized</population>
      <group_list>
        <group group_id="B1">
          <title>CERC-501</title>
          <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</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="45"/>
            <count group_id="B2" value="44"/>
            <count group_id="B3" value="89"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="89"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
            </class>
          </class_list>
        </measure>
        <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="40.7" spread="13.30"/>
                    <measurement group_id="B2" value="38.2" spread="13.02"/>
                    <measurement group_id="B3" value="39.5" spread="13.15"/>
                  </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="29"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </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="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI</title>
        <description>Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.</description>
        <time_frame>baseline, Week 8</time_frame>
        <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>CERC-501</title>
            <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI</title>
          <description>Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.</description>
          <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
          <units>Z score</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.718" lower_limit="0.487" upper_limit="0.950"/>
                    <measurement group_id="O2" value="0.331" lower_limit="0.103" upper_limit="0.559"/>
                  </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>0.0095</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)</title>
        <description>To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). A single value was calculated for the average over 8 weeks. The SHAPS is a well-validated 14-item questionnaire used to assess anhedonia. It asks participants to agree or disagree with statements of hedonic response in pleasurable situations. Four responses are possible: Strongly disagree, Disagree, Agree, or Strongly agree. Each item is worded so that higher scores indicate greater pleasure capacity. A total score is derived by summing the responses to each item. Items answered &quot;strongly agree&quot; are coded as &quot;1&quot;, while &quot;strongly disagree&quot; are coded a score of &quot;4.&quot; Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.</description>
        <time_frame>8 weeks</time_frame>
        <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>CERC-501</title>
            <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)</title>
          <description>To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). A single value was calculated for the average over 8 weeks. The SHAPS is a well-validated 14-item questionnaire used to assess anhedonia. It asks participants to agree or disagree with statements of hedonic response in pleasurable situations. Four responses are possible: Strongly disagree, Disagree, Agree, or Strongly agree. Each item is worded so that higher scores indicate greater pleasure capacity. A total score is derived by summing the responses to each item. Items answered &quot;strongly agree&quot; are coded as &quot;1&quot;, while &quot;strongly disagree&quot; are coded a score of &quot;4.&quot; Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.</description>
          <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.777" lower_limit="29.547" upper_limit="32.007"/>
                    <measurement group_id="O2" value="32.363" lower_limit="31.157" upper_limit="33.568"/>
                  </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>0.0345</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task</title>
        <description>To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function (level of reward learning). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli</description>
        <time_frame>baseline, Week 8</time_frame>
        <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>CERC-501</title>
            <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task</title>
          <description>To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function (level of reward learning). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli</description>
          <population>The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.</population>
          <units>Ratio (Response Bias Score)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.034" lower_limit="-0.019" upper_limit="0.087"/>
                    <measurement group_id="O2" value="0.019" lower_limit="-0.030" upper_limit="0.068"/>
                  </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>0.430</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time of consent through 12 weeks for all subjects.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CERC-501</title>
          <description>Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks&#xD;
CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Oral daily administration of 10 mg placebo for 8 weeks&#xD;
placebo: oral dosing of 10 mg placebo daily for 8 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <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="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.1</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="34" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vission Blurred</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Anal pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Costochondritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Coordination Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Disturbance in Attention</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Depressive symptom</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Initial insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Intentional self-injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Middle insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Mood altered</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Self-injurious ideation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Urinary track infeciton</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Libido decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Menstruation irregular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Amenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Pharyngeal erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Puritus</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kathy Hijek, Associate Director of Clinical Operations</name_or_title>
      <organization>Duke Clnical Research Institute</organization>
      <phone>919-668-8700</phone>
      <email>kathy.hijek@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02218736
org study id: Pro00052485
secondary id: HHSN271201200006I
nct id: NCT02218736
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The available treatment for patients with mood and anxiety disorders have significant
      limitations (Rush, 2007; Denys and de Geus, 2005). There is a need to develop new treatments
      for people with these disorders. Many research studies carried out in animals and a few
      preliminary studies carried out in humans suggest that medications which block kappa opioid
      receptors (KOR) have potential for being effective new treatments for patients with mood and
      anxiety spectrum disorders. These medications have shown particular promise for improving one
      important type of difficulty experienced by many patients who suffer from mood and anxiety
      spectrum disorders referred to as anhedonia, which is an impairment in reward-related
      function. In this study we will test the hypothesis that KOR antagonism is a promising means
      of improving anhedonia in patients with mood and anxiety spectrum disorders. We will do so by
      evaluating whether we can establish Proof of Concept (POC) that a relatively selective KOR
      antagonist, CERC-501 (formerly known as LY2456302), engages neural circuits involved in
      mediating reward-related function in patients with mood and anxiety spectrum disorders with
      anhedonia. We are attempting to establish POC in this study in order to determine whether
      there is a sufficient basis for pursuing future work evaluating whether KOR antagonism has
      therapeutic effects on clinical and behavioral measures of reward-related functioning.
FAST-MAS addresses an important problem and critical barrier to progress in Mood and Anxiety
      Spectrum Disorders and if the aims of the project are achieved, FAST-MAS could shift
      scientific knowledge, technical capacity, and clinical practice in a positive direction.

      The Mood and Anxiety Spectrum disorders are both extremely common and associated with
      significant morbidity and mortality and, as such, represent an important public health
      problem in the United States.

      The mood disorders include the following diagnostic entities: major depressive disorder
      (MDD), bipolar disorder (including subtypes of mania, mixed state, and depressed, as well as
      types I and II), and dysthymic disorder. Available epidemiologic data suggest that the
      prevalence of these mood disorders is extremely high among adults in the United States,
      approaching 10%. Among the mood disorders, MDD has high lifetime prevalence, with recent
      estimates up to 16%. According to the World Health Organization (WHO), MDD is currently the
      leading cause of disability with the greatest burden of illness in developed countries and
      the third most common cause of disability worldwide. MDD is life shortening due to both
      suicide and its association with increased mortality from other medical conditions. It is
      also a highly recurrent condition with between 50% and 75% of persons diagnosed with MDD
      experiencing more than one episode. Bipolar Disorder is also a highly recurrent condition.
      The lifetime prevalence of bipolar disorder has been estimated to be approximately 3.4% in
      the World Health Survey Initiative. Approximately 60% of affected individuals experience
      severe or very severe role impairment based on the Sheehan Disability Scale and, like MDD,
      bipolar disorder is associated with significant suicide risk.

      The anxiety disorders are also very common and associated with significant adverse impact on
      affected individuals and society. These disorders include the following diagnostic entities:
      generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder, social
      phobia, specific phobias, and post-traumatic stress disorder (PTSD). As a group, these
      conditions affect approximately 18% of adults in a given year and they are associated with
      significant co-morbidities and adverse consequences. Of the anxiety disorders, GAD appears to
      be associated with the greatest per patient cost and disability with a degree of disability
      comparable to that of MDD and comparable to chronic medical conditions such as arthritis,
      diabetes, and peptic ulcer disease. It affects approximately 6.8 million adults in the U.S.
      and is a highly chronic condition. Panic disorder affects about 6 million American adults and
      is twice as common in women as men. Panic disorder is also highly disabling and often chronic
      and even mild forms of this disorder are linked to significantly increased impairment in
      function and quality of life as well as a number of comorbidities. Approximately 2.2 million
      adults in the U.S. are affected by obsessive-compulsive disorder and this disorder is often
      accompanied by psychiatric comorbidities. Roughly half of individuals with this condition
      have a chronic unremitting course which is associated with significant disability and
      morbidity. Social phobia, also known as social anxiety disorder, is seen in roughly 15
      million adults in the U.S. and is often associated with MDD or other anxiety disorders. It is
      generally a chronic condition that leads to a great degree of disability due to substantial
      impairment in social, educational, and occupational function. Approximately 8 million adults
      in the U.S. experience PTSD and approximately 12% of the population have PTSD at some point
      in their lives and affected individuals frequently experience associated MDD, other anxiety
      disorders and substance use problems. The level of disability associated with this condition
      tends to be quite high and includes impairment in social and occupational function and
      quality of life. There are also substantial financial and social costs associated with PTSD
      due to increased hospitalization rates, suicidality, and substance use problem.

      Mood disorders and anxiety disorders are highly prevalent conditions, many of which are
      chronic, nearly all of which are associated with substantial comorbidities, disability and
      impairment and some are associated with an increased risk for mortality. Despite the
      availability of many pharmacologic, psychotherapeutic, brain stimulation, and combination
      treatment options available to clinicians, many patients with Mood and Anxiety Spectrum
      Disorders respond poorly to treatment. In light of the impairments, costs, and risks of these
      disorders, the limitations of the available treatments represents an enormous burden to
      public health and speak strongly to the need for new treatments for these conditions as well
      as novel methodologies of treatment development that are not only faster than existing
      methodologies but which also promote new ways of thinking about these disorders and their
      treatment and capitalize on recent and ongoing developments in basic science.

      This study will be a six-site randomized, double-blind, PBO (placebo) -controlled,
      parallel-group mono-therapy study to assess the effects of CERC-501 (formerly known as
      LY2456302) compared to PBO in adults age 21-65 years with mood and anxiety spectrum
      disorders. We will recruit a total of 90 subjects, of which 45 will be randomized to CERC-501
      and 45 to placebo for 8 weeks of treatment
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI
time frame: baseline, Week 8
description: Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.
measure: Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)
time frame: 8 weeks
description: To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). A single value was calculated for the average over 8 weeks. The SHAPS is a well-validated 14-item questionnaire used to assess anhedonia. It asks participants to agree or disagree with statements of hedonic response in pleasurable situations. Four responses are possible: Strongly disagree, Disagree, Agree, or Strongly agree. Each item is worded so that higher scores indicate greater pleasure capacity. A total score is derived by summing the responses to each item. Items answered "strongly agree" are coded as "1", while "strongly disagree" are coded a score of "4." Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
measure: Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task
time frame: baseline, Week 8
description: To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function (level of reward learning). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli
arm group label: CERC-501
arm group type: Experimental
description: Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral daily administration of 10 mg placebo for 8 weeks
intervention type: Drug
intervention name: CERC-501
description: Oral dosing of 10 mg CERC-501 daily for 8 weeks
arm group label: CERC-501
other name: Kappa Opioid Receptor Antagonist; LY2456302
intervention type: Drug
intervention name: placebo
description: oral dosing of 10 mg placebo daily for 8 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
last name: Richard D Weiner, MD, PhD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Rorick-Kehn LM, Witkin JM, Statnick MA, Eberle EL, McKinzie JH, Kahl SD, Forster BM, Wong CJ, Li X, Crile RS, Shaw DB, Sahr AE, Adams BL, Quimby SJ, Diaz N, Jimenez A, Pedregal C, Mitch CH, Knopp KL, Anderson WH, Cramer JW, McKinzie DL. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014 Feb;77:131-44. doi: 10.1016/j.neuropharm.2013.09.021. Epub 2013 Sep 23.
PMID: 24071566
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Phobic Disorders
mesh term: Aticaprant
mesh term: Narcotic Antagonists
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 