<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/NCT03818399</url>
  </required_header>
  <id_info>
    <org_study_id>HM20015109</org_study_id>
    <nct_id>NCT03818399</nct_id>
  </id_info>
  <brief_title>Virginia Opioid Overdose Treatment InitiatVE</brief_title>
  <acronym>VOTIVE</acronym>
  <official_title>Virginia Opioid Overdose Treatment InitiatVE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Indivior, PLC.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 3b, open-label study in patients that present to the ED for an opioid OD and&#xD;
      receive treatment with an opioid antagonist. The study is designed to determine effect of&#xD;
      SUBLOCADE on repeat overdose and death compared to historical control data.&#xD;
&#xD;
      The study will assess subjects that receive acute administration of SUBOXONE sublingual film&#xD;
      in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral&#xD;
      to an affiliated outpatient treatment clinic, compared to historical control data from&#xD;
      electronic health records.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will assess subjects that receive acute administration of SUBOXONE sublingual film&#xD;
      in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral&#xD;
      to an affiliated outpatient treatment clinic, compared to historical control data from VCU&#xD;
      electronic health records. The affiliated clinic will agree to see the subject on arrival at&#xD;
      the clinic during normal clinic hours.&#xD;
&#xD;
      Patients presenting to the ED for an opioid overdose (OD) who received treatment with an&#xD;
      opioid antagonist and are considered clinically stable and alert will be approached regarding&#xD;
      interest in study participation. Written informed consent will only be obtained if the&#xD;
      patient's judgement is intact as determined clinically by the investigator or a medically&#xD;
      qualified sub-investigator or research nurse. This OD will be considered the index OD.&#xD;
&#xD;
      Subjects will be given the opportunity to participate in an optional pharmacogenetics (PGx)&#xD;
      sub-study.&#xD;
&#xD;
      The subject will receive referral to an outpatient treatment clinic affiliated with the&#xD;
      hospital system in which the ED resides.&#xD;
&#xD;
      Once subjects arrive at the treatment clinic, they will continue to receive SUBLOCADE for 6&#xD;
      months. All subjects will receive site standard psychosocial therapy at least weekly during&#xD;
      the first 3 months of treatment, and twice monthly thereafter if clinically stable.&#xD;
&#xD;
      All subjects will complete an End of Treatment (EOT) / Early Termination (ET) visit 28 days&#xD;
      after their last injection of SUBLOCADE. Within 3 months prior to or at the EOT visit, the&#xD;
      investigator or a medically qualified sub-investigator will discuss the subject's available&#xD;
      treatment options and arrange referral. All subjects will receive a safety follow-up&#xD;
      telephone call, 30 days after their EOT/ET visit to assess AEs, SAEs, pregnancy status (if&#xD;
      applicable) and concomitant medications. Subjects who decline to continue in medication&#xD;
      assisted treatment (MAT) will receive monthly safety follow-up phone calls for an additional&#xD;
      5 months (6 months total) to assess SAEs, pregnancy status (if applicable) and concomitant&#xD;
      medications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to a financial business decision by the company supporting the research study (Indivior).&#xD;
    The decision was not due to adverse events, safety reasons, or scientific reasons, but was a&#xD;
    business decision.&#xD;
  </why_stopped>
  <start_date type="Actual">January 4, 2019</start_date>
  <completion_date type="Actual">February 24, 2021</completion_date>
  <primary_completion_date type="Actual">February 24, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Repeat OD or Opioid-related Death</measure>
    <time_frame>6 months</time_frame>
    <description>Repeat OD or opioid-related death will be measured from electronic medical records and state death registries</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment Engagement</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Opioid Craving</measure>
    <time_frame>6 months</time_frame>
    <description>Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)</description>
  </other_outcome>
  <other_outcome>
    <measure>Illicit Opioid Use</measure>
    <time_frame>6 months</time_frame>
    <description>Illicit opioid use as measured by urine drug screen (UDS) results.</description>
  </other_outcome>
  <other_outcome>
    <measure>Genetic Predictors of Treatment Response</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects</description>
  </other_outcome>
  <other_outcome>
    <measure>Healthcare Resource Utilization</measure>
    <time_frame>6 months</time_frame>
    <description>Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls</description>
  </other_outcome>
  <other_outcome>
    <measure>Treatment Effectiveness and Employment</measure>
    <time_frame>6 months</time_frame>
    <description>Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)</description>
  </other_outcome>
  <other_outcome>
    <measure>Medication Satisfaction</measure>
    <time_frame>6 months</time_frame>
    <description>measured by the Medication Satisfaction Questionnaire (MSQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Employment, Presentism and Absenteeism</measure>
    <time_frame>6 months</time_frame>
    <description>assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Opioid Use Disorder</condition>
  <arm_group>
    <arm_group_label>overdose patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SUBLOCADE</intervention_name>
    <description>SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
    <arm_group_label>overdose patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed the informed consent form (ICF) and have the ability to comply with the&#xD;
             requirements and restrictions listed therein.&#xD;
&#xD;
          -  Age: ≥ 18 years at time of executing the ICF.&#xD;
&#xD;
          -  Currently meets DSM-5 criteria for moderate to severe opioid use disorder.&#xD;
&#xD;
          -  Must have Clinical Opioid Withdrawal Scale (COWS) score of &gt;8 to be eligible for&#xD;
             SUBOXONE dose.&#xD;
&#xD;
          -  Is clinically stable (respiratory rate [RR] ≥ 12, pulse oximetry &gt; 95%, Glasgow Coma&#xD;
             Scale [GCS] score of 15) and suitable for the trial in investigator or designee's&#xD;
             judgement.&#xD;
&#xD;
          -  Agrees not to take any buprenorphine products other than those administered during the&#xD;
             current study throughout participation in the study.&#xD;
&#xD;
          -  Negative urine pregnancy test for females.&#xD;
&#xD;
          -  Vital signs (blood pressure, heart rate, temperature) considered within normal limits&#xD;
             or non-clinically significant elevation, as assessed by treating physician.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis, other than opioid use disorder, requiring chronic opioid treatment.&#xD;
&#xD;
          -  Active suicidal ideation in opinion of investigator or designee.&#xD;
&#xD;
          -  Female subject that is lactating, pregnant or planning to become pregnant during their&#xD;
             participation in the study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements or&#xD;
             compromise the ability of the subject to provide written informed consent, signs of&#xD;
             opioid toxicity more than 2 hours from naloxone administration or subjects with&#xD;
             evidence of pulmonary edema.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to SUBOXONE.&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator would interfere with&#xD;
             interpretation of subject safety or study results.&#xD;
&#xD;
          -  Currently receiving medication assisted treatment (MAT) for opioid use disorder (OUD)&#xD;
             (e.g. methadone, buprenorphine) or received MAT as a treatment for OUD within 30 days&#xD;
             prior to consent.&#xD;
&#xD;
          -  Concurrent treatment with another investigational agent.&#xD;
&#xD;
          -  Concurrent enrolment in another clinical study, or observational study that includes&#xD;
             MAT.&#xD;
&#xD;
          -  Treatment for opioid use disorder required by court order.&#xD;
&#xD;
          -  Current or pending incarceration/ legal action that could affect participation or&#xD;
             compliance in the study.&#xD;
&#xD;
          -  Subjects who are unable, in the opinion of the investigator, to comply fully with the&#xD;
             study requirements.&#xD;
&#xD;
          -  Less than 48-72 hours since last use of long acting opioids (e.g., methadone), by&#xD;
             self-report.&#xD;
&#xD;
          -  Current intoxication with benzodiazepines or alcohol.&#xD;
&#xD;
          -  Meet current DSM-5 diagnosis for severe Benzodiazepine or Alcohol Use Disorder, or&#xD;
             endorse benzodiazepine or alcohol withdrawal symptoms.&#xD;
&#xD;
          -  Current illicit opioid users who endorse regular use of long acting opioids (e.g.&#xD;
             methadone).&#xD;
&#xD;
          -  Total bilirubin ≥ 1.5x the upper limit of normal (ULN), alanine aminotransferase (ALT)&#xD;
             ≥3xULN, aspartate aminotransferase (AST) ≥ 3xULN, serum creatinine &gt; 2xULN,&#xD;
             international normalized ratio (INR) &gt;1.5xULN&#xD;
&#xD;
          -  Patients with a history of Long QT Syndrome or an immediate family member with this&#xD;
             condition or those taking Class lA antiarrhythmic medications (e.g., quinidine,&#xD;
             procainamide, disopyramide) or Class Ill antiarrhythmic medications (e.g., sotalol,&#xD;
             amiodarone, or other mediations that prolong the QT interval.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frederick G Moeller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <results_first_submitted>February 24, 2022</results_first_submitted>
  <results_first_submitted_qc>April 8, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 5, 2022</results_first_posted>
  <last_update_submitted>April 8, 2022</last_update_submitted>
  <last_update_submitted_qc>April 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Opiate Overdose</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03818399/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Overdose Patients</title>
          <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.&#xD;
SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Overdose Patients</title>
          <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.&#xD;
SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.4" spread="12.1"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Repeat OD or Opioid-related Death</title>
        <description>Repeat OD or opioid-related death will be measured from electronic medical records and state death registries</description>
        <time_frame>6 months</time_frame>
        <population>Because repeat OD or opioid-related death is measured from electronic medical records and state death registries, data was collected on all participants even if they did not complete the study</population>
        <group_list>
          <group group_id="O1">
            <title>Overdose Patients</title>
            <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.&#xD;
SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Repeat OD or Opioid-related Death</title>
          <description>Repeat OD or opioid-related death will be measured from electronic medical records and state death registries</description>
          <population>Because repeat OD or opioid-related death is measured from electronic medical records and state death registries, data was collected on all participants even if they did not complete the study</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Prevalence of repeat opioid-related overdose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prevalence opioid-related death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Engagement</title>
        <description>Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.</description>
        <time_frame>3 and 6 months</time_frame>
        <population>An intent to treat model was used so data from all participants, even those who did not complete, was analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Overdose Patients</title>
            <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.&#xD;
SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Engagement</title>
          <description>Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.</description>
          <population>An intent to treat model was used so data from all participants, even those who did not complete, was analyzed</population>
          <units>visits</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>3 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="7.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3" spread="9.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Opioid Craving</title>
        <description>Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Illicit Opioid Use</title>
        <description>Illicit opioid use as measured by urine drug screen (UDS) results.</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Genetic Predictors of Treatment Response</title>
        <description>Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Healthcare Resource Utilization</title>
        <description>Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Treatment Effectiveness and Employment</title>
        <description>Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Medication Satisfaction</title>
        <description>measured by the Medication Satisfaction Questionnaire (MSQ)</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Employment, Presentism and Absenteeism</title>
        <description>assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)</description>
        <time_frame>6 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Overdose Patients</title>
          <description>subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.&#xD;
SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Inpatient psychiatric treatment for schizoaffective disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="11" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Lower extremity edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Reduced appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Withdrawal symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Leg muscle cramps after fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Acute neck strain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Acute back pain from moving</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Chronic back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Chronic neck pain associated with arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Acute left knee pain with comorbid arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Inflammation at injection site</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Lip abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Maculopapular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </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>Roy Sabo, PhD</name_or_title>
      <organization>Virginia Commonwealth University</organization>
      <phone>804-828-3047</phone>
      <email>roy.sabo@vcuhealth.org</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/NCT03818399
org study id: HM20015109
nct id: NCT03818399
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 3b, open-label study in patients that present to the ED for an opioid OD and
      receive treatment with an opioid antagonist. The study is designed to determine effect of
      SUBLOCADE on repeat overdose and death compared to historical control data.

      The study will assess subjects that receive acute administration of SUBOXONE sublingual film
      in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral
      to an affiliated outpatient treatment clinic, compared to historical control data from
      electronic health records.
The study will assess subjects that receive acute administration of SUBOXONE sublingual film
      in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral
      to an affiliated outpatient treatment clinic, compared to historical control data from VCU
      electronic health records. The affiliated clinic will agree to see the subject on arrival at
      the clinic during normal clinic hours.

      Patients presenting to the ED for an opioid overdose (OD) who received treatment with an
      opioid antagonist and are considered clinically stable and alert will be approached regarding
      interest in study participation. Written informed consent will only be obtained if the
      patient's judgement is intact as determined clinically by the investigator or a medically
      qualified sub-investigator or research nurse. This OD will be considered the index OD.

      Subjects will be given the opportunity to participate in an optional pharmacogenetics (PGx)
      sub-study.

      The subject will receive referral to an outpatient treatment clinic affiliated with the
      hospital system in which the ED resides.

      Once subjects arrive at the treatment clinic, they will continue to receive SUBLOCADE for 6
      months. All subjects will receive site standard psychosocial therapy at least weekly during
      the first 3 months of treatment, and twice monthly thereafter if clinically stable.

      All subjects will complete an End of Treatment (EOT) / Early Termination (ET) visit 28 days
      after their last injection of SUBLOCADE. Within 3 months prior to or at the EOT visit, the
      investigator or a medically qualified sub-investigator will discuss the subject's available
      treatment options and arrange referral. All subjects will receive a safety follow-up
      telephone call, 30 days after their EOT/ET visit to assess AEs, SAEs, pregnancy status (if
      applicable) and concomitant medications. Subjects who decline to continue in medication
      assisted treatment (MAT) will receive monthly safety follow-up phone calls for an additional
      5 months (6 months total) to assess SAEs, pregnancy status (if applicable) and concomitant
      medications.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Repeat OD or Opioid-related Death
time frame: 6 months
description: Repeat OD or opioid-related death will be measured from electronic medical records and state death registries
measure: Treatment Engagement
time frame: 3 and 6 months
description: Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.
measure: Opioid Craving
time frame: 6 months
description: Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)
measure: Illicit Opioid Use
time frame: 6 months
description: Illicit opioid use as measured by urine drug screen (UDS) results.
measure: Genetic Predictors of Treatment Response
time frame: 6 months
description: Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects
measure: Healthcare Resource Utilization
time frame: 6 months
description: Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls
measure: Treatment Effectiveness and Employment
time frame: 6 months
description: Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)
measure: Medication Satisfaction
time frame: 6 months
description: measured by the Medication Satisfaction Questionnaire (MSQ)
measure: Employment, Presentism and Absenteeism
time frame: 6 months
description: assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)
arm group label: overdose patients
arm group type: Experimental
description: subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.
intervention type: Drug
intervention name: SUBLOCADE
description: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
arm group label: overdose patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frederick G Moeller, MD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Opiate Overdose
mesh term: Buprenorphine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 