<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/NCT04501874</url>
  </required_header>
  <id_info>
    <org_study_id>ERL-003</org_study_id>
    <secondary_id>5U01DA038879-03</secondary_id>
    <nct_id>NCT04501874</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate EMB 001 in Subjects With Cocaine Use Disorder</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Safety and Efficacy of EMB 001 in Subjects With Moderate-to-Severe Cocaine Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Embera NeuroTherapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Embera NeuroTherapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      EMB-001 is a combination of 2 drugs: the cortisol synthesis inhibitor, metyrapone&#xD;
      (Metopirone®), and the benzodiazepine receptor agonist, oxazepam (original trade name Serax®;&#xD;
      now marketed as oxazepam (generic) only).&#xD;
&#xD;
      This is a Phase 2 study in approximately 80 adult subjects with moderate-to-severe Cocaine&#xD;
      Use Disorder (CUD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, study&#xD;
      to compare the safety and efficacy of EMB-001 with a placebo control in approximately 80&#xD;
      subjects with moderate-to-severe CUD. Subjects will receive investigational medicinal product&#xD;
      (IMP) during a 12-week, double-blind Treatment Period (Week 2 through Week 13) and a 1-week,&#xD;
      double-blind Taper Period (Week 14).&#xD;
&#xD;
      After undergoing study procedures during the Screening and Baseline Periods, subjects who&#xD;
      meet inclusion and exclusion criteria will then be randomized in a 1:1 ratio (n=40/arm) to&#xD;
      one of the following for the Treatment Period (weeks 2 - 13) on Study Day 8:&#xD;
&#xD;
        -  EMB-001 720 mg metyrapone/24 mg oxazepam mg BID, for a total daily dose of 1440 mg&#xD;
           metyrapone and 48 mg oxazepam (Active Group)&#xD;
&#xD;
        -  Placebo BID, (Placebo Group)&#xD;
&#xD;
      During the Taper Period (week 14), subjects in the Active Group will receive EMB-001 240/8 mg&#xD;
      BID; and the Placebo Group will continue to receive placebo. Both groups will change from&#xD;
      taking three capsules BID (twice daily) to one capsule BID (twice daily).&#xD;
&#xD;
      There will be a follow-up visit for safety assessments at Week 18.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 29, 2020</start_date>
  <completion_date type="Actual">October 15, 2022</completion_date>
  <primary_completion_date type="Actual">July 27, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Continuous Abstinence from Cocaine Use</measure>
    <time_frame>Week 11 to Week 13</time_frame>
    <description>The Primary Endpoint is the Proportion of Subjects That Successfully Achieve Abstinence From Cocaine During the Last Three Weeks of Treatment using the Timeline Follow Back; days of abstinence, confirmed by Urine benzoylecgonine (BE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
    <time_frame>13 weeks</time_frame>
    <description>Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in cocaine-use days</measure>
    <time_frame>Week 2 to Week 13</time_frame>
    <description>Self-report weekly cocaine non-use days by Timeline Follow-Back</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine confirmation of cocaine use</measure>
    <time_frame>Week 2 to Week 13</time_frame>
    <description>Qualitative urine BE levels twice per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in total Cocaine Craving Questionnaire-Brief score</measure>
    <time_frame>Week 2 to Week 13</time_frame>
    <description>The Cocaine Craving Questionnaire-Brief (CCQ-B) assesses current cocaine craving in routine clinical practice. The CCQ-B is a 10 item questionnaire and items are scored on a one to seven scale. Total responses are then divided by 10 to achieve a total craving score between 1.0 (least craving) to 7.0 (most craving).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Cocaine Use Disorder</condition>
  <arm_group>
    <arm_group_label>EMB-001 Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EMB-001 Combination product of 720 mg metyrapone/24 mg oxazepam mg by mouth twice per day for 12 weeks followed by a 1 week taper</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EMB-001 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>EMB-001 Placebo by mouth twice per day for 12 weeks followed by a 1 week taper</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EMB-001</intervention_name>
    <description>720 mg metyrapone/24 mg oxazepam mg BID</description>
    <arm_group_label>EMB-001 Active</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EMB-001 Placebo</intervention_name>
    <description>Inactive comparator</description>
    <arm_group_label>EMB-001 Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Provide written informed consent prior to any study procedures&#xD;
&#xD;
          -  18 to 65 years of age&#xD;
&#xD;
          -  DSM-5 diagnosis of moderate-to-severe CUD&#xD;
&#xD;
          -  Seeking treatment for CUD. Subjects with past rehabilitation attempts are eligible if&#xD;
             the most recent rehabilitation attempt ended at least 30 days prior to Screening&#xD;
&#xD;
          -  Female subjects must be of non-childbearing potential&#xD;
&#xD;
          -  Male subjects must agree to use accepted contraceptive regimens during the study and&#xD;
             for at least 90 days after the last dose of the study drug&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any significant current medical conditions&#xD;
&#xD;
          -  Known hypersensitivity to or intolerance of oxazepam, metyrapone, or any&#xD;
             benzodiazepine, or severe hypersensitivity reaction (e.g., angioedema) to any drug&#xD;
&#xD;
          -  Heightened likelihood of having adrenal insufficiency in the investigator's or&#xD;
             designees' opinion&#xD;
&#xD;
          -  Current court-mandated treatment requirement for a substance-use disorder&#xD;
&#xD;
          -  Current DSM-5 moderate-to-severe substance use disorder, other than CUD, tobacco or&#xD;
             caffeine&#xD;
&#xD;
          -  Current DSM-5 opioid or benzodiazepine use disorder of any severity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female subjects must be of non-childbearing potential.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce McCarthy, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Embera NeuroTherapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pacific Treatment and Research Center, Department of Psychiatry, University of California, San Diego, School of Medicine</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Segal Trials</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U PENN- Perelman School of Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kablinger AS, Lindner MA, Casso S, Hefti F, DeMuth G, Fox BS, McNair LA, McCarthy BG, Goeders NE. Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study. J Psychopharmacol. 2012 Jul;26(7):973-81. doi: 10.1177/0269881111430745. Epub 2012 Jan 11.</citation>
    <PMID>22236504</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cocaine</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Every three months, the NIDA DSMB will convene to review the overall safety data, as well as data on safety summarized by treatment condition. As per NIH guidelines, the objective of these reviews will be to determine whether continued conduct of the trial poses any undue risk for participants. Blinded data tables, figures and/or listings will be provided to the Data Safety Monitoring Board (DSMB).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Every three months- blinded results</ipd_time_frame>
    <ipd_access_criteria>A DSMB report is prepared an submitted via NIDA</ipd_access_criteria>
  </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/NCT04501874
org study id: ERL-003
secondary id: 5U01DA038879-03
nct id: NCT04501874
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
EMB-001 is a combination of 2 drugs: the cortisol synthesis inhibitor, metyrapone
      (Metopirone®), and the benzodiazepine receptor agonist, oxazepam (original trade name Serax®;
      now marketed as oxazepam (generic) only).

      This is a Phase 2 study in approximately 80 adult subjects with moderate-to-severe Cocaine
      Use Disorder (CUD).
This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, study
      to compare the safety and efficacy of EMB-001 with a placebo control in approximately 80
      subjects with moderate-to-severe CUD. Subjects will receive investigational medicinal product
      (IMP) during a 12-week, double-blind Treatment Period (Week 2 through Week 13) and a 1-week,
      double-blind Taper Period (Week 14).

      After undergoing study procedures during the Screening and Baseline Periods, subjects who
      meet inclusion and exclusion criteria will then be randomized in a 1:1 ratio (n=40/arm) to
      one of the following for the Treatment Period (weeks 2 - 13) on Study Day 8:

        -  EMB-001 720 mg metyrapone/24 mg oxazepam mg BID, for a total daily dose of 1440 mg
           metyrapone and 48 mg oxazepam (Active Group)

        -  Placebo BID, (Placebo Group)

      During the Taper Period (week 14), subjects in the Active Group will receive EMB-001 240/8 mg
      BID; and the Placebo Group will continue to receive placebo. Both groups will change from
      taking three capsules BID (twice daily) to one capsule BID (twice daily).

      There will be a follow-up visit for safety assessments at Week 18.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Continuous Abstinence from Cocaine Use
time frame: Week 11 to Week 13
description: The Primary Endpoint is the Proportion of Subjects That Successfully Achieve Abstinence From Cocaine During the Last Three Weeks of Treatment using the Timeline Follow Back; days of abstinence, confirmed by Urine benzoylecgonine (BE)
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
time frame: 13 weeks
description: Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts.
measure: Reduction in cocaine-use days
time frame: Week 2 to Week 13
description: Self-report weekly cocaine non-use days by Timeline Follow-Back
measure: Urine confirmation of cocaine use
time frame: Week 2 to Week 13
description: Qualitative urine BE levels twice per week
measure: Reduction in total Cocaine Craving Questionnaire-Brief score
time frame: Week 2 to Week 13
description: The Cocaine Craving Questionnaire-Brief (CCQ-B) assesses current cocaine craving in routine clinical practice. The CCQ-B is a 10 item questionnaire and items are scored on a one to seven scale. Total responses are then divided by 10 to achieve a total craving score between 1.0 (least craving) to 7.0 (most craving).
arm group label: EMB-001 Active
arm group type: Active Comparator
description: EMB-001 Combination product of 720 mg metyrapone/24 mg oxazepam mg by mouth twice per day for 12 weeks followed by a 1 week taper
arm group label: EMB-001 Placebo
arm group type: Placebo Comparator
description: EMB-001 Placebo by mouth twice per day for 12 weeks followed by a 1 week taper
intervention type: Drug
intervention name: EMB-001
description: 720 mg metyrapone/24 mg oxazepam mg BID
arm group label: EMB-001 Active
intervention type: Drug
intervention name: EMB-001 Placebo
description: Inactive comparator
arm group label: EMB-001 Placebo
criteria: 
gender: All
gender based: Yes
gender description: Female subjects must be of non-childbearing potential.
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Bruce McCarthy, MD
role: Study Chair
affiliation: Embera NeuroTherapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Kablinger AS, Lindner MA, Casso S, Hefti F, DeMuth G, Fox BS, McNair LA, McCarthy BG, Goeders NE. Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study. J Psychopharmacol. 2012 Jul;26(7):973-81. doi: 10.1177/0269881111430745. Epub 2012 Jan 11.
PMID: 22236504
responsible party type: Sponsor
sharing ipd: Yes
ipd description: Every three months, the NIDA DSMB will convene to review the overall safety data, as well as data on safety summarized by treatment condition. As per NIH guidelines, the objective of these reviews will be to determine whether continued conduct of the trial poses any undue risk for participants. Blinded data tables, figures and/or listings will be provided to the Data Safety Monitoring Board (DSMB).
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: Every three months- blinded results
ipd access criteria: A DSMB report is prepared an submitted via NIDA