<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/NCT03752528</url>
  </required_header>
  <id_info>
    <org_study_id>INDV-6000-402</org_study_id>
    <nct_id>NCT03752528</nct_id>
  </id_info>
  <brief_title>Evaluation of Long-term Buprenorphine Plasma Exposure</brief_title>
  <official_title>Evaluation of Long-term Buprenorphine Plasma Exposure in Subjects Who Received at Least 2 Subcutaneous (SC) Injections of Extended-release Buprenorphine (SUBLOCADE™) in Phase III Studies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indivior Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indivior Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study objective is to characterise the long-term plasma exposure to buprenorphine after&#xD;
      stopping SUBLOCADE treatment. There are no interventions planned.&#xD;
&#xD;
      This multicentre investigation will enroll participants from Study RB-US-13-0003&#xD;
      (NCT02510014) or both Studies RB-US-13-0003 and INDV-6000-301 (NCT02896296) and who received&#xD;
      at least 2 subcutaneous (SC) injections of SUBLOCADE.&#xD;
&#xD;
      There are two parts to the study:&#xD;
&#xD;
      Part A consists of a single visit during which urine samples are collected to measure free&#xD;
      buprenorphine and free norbuprenorphine concentrations; qualitative urine drug samples (UDS)&#xD;
      for opioids, including buprenorphine; quantitative UDS for buprenorphine, norbuprenorphine&#xD;
      and naloxone; and determination of creatinine concentration. Blood samples are collected for&#xD;
      the determination of buprenorphine and norbuprenorphine plasma concentrations.&#xD;
&#xD;
      Results on the quantitative UDS performed in Part A determine enrollment in Part B:&#xD;
      participants who provide a quantifiable (i.e., positive) result for buprenorphine and/or&#xD;
      norbuprenorphine and a non-quantifiable (i.e., negative) result for naloxone meet&#xD;
      continuation criteria to move on to Part B if Part B is still open to enrolment. Part B&#xD;
      consists of two visits 30 days apart in which the same tests are run as were done in Part A.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data indicate that after discontinuing SUBLOCADE patients may have detectable concentrations&#xD;
      of buprenorphine in plasma and urine for 12 months or longer. Previous Phase II/III studies&#xD;
      did not evaluate the pharmacokinetics (PK) of buprenorphine beyond 2 months after the last&#xD;
      injection; this study will characterize the long-term plasma exposure starting at least 12&#xD;
      months after the last injection. The study will also assess relationships between plasma drug&#xD;
      concentrations, free drug concentrations in urine and urine drug screen (UDS) results in&#xD;
      order to provide refined guidance to patients and physicians with respect to long-term&#xD;
      exposure to buprenorphine after stopping SUBLOCADE treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 19, 2019</start_date>
  <completion_date type="Actual">July 18, 2019</completion_date>
  <primary_completion_date type="Actual">July 18, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B</measure>
    <time_frame>Days 1, 30, 60</time_frame>
    <description>The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B</measure>
    <time_frame>Days 1, 30, 60</time_frame>
    <description>The quantitative UDS measures both buprenorphine and its glucuronide, or both norbuprenorphine and its glucuronide, with an LLOQ of 2 ng/mL. It is typically used by physicians for the confirmation of a positive result on the qualitative UDS.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</measure>
    <time_frame>Days 1, 30, 60</time_frame>
    <description>The urine free drug test only measures the &quot;free&quot; buprenorphine and &quot;free&quot; norbuprenorphine (without their glucuronides) with an LLOQ of 0.02 ng/mL.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</measure>
    <time_frame>Days 1, 30, 60</time_frame>
    <description>A sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was used to assess the plasma exposure to buprenorphine and norbuprenorphine, its major metabolite. The LLOQ was 0.02 ng/mL for both analytes, which is much lower than the LLOQ of plasma/serum assays conducted by diagnostic laboratories.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">53</enrollment>
  <condition>Opioid-use Disorder</condition>
  <arm_group>
    <arm_group_label>Part A Cohort</arm_group_label>
    <description>Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B Cohort</arm_group_label>
    <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Visits 2 and 3) which are conducted approximately 30 days apart during which blood and urine samples are collected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood sample collection</intervention_name>
    <description>Determination of buprenorphine and norbuprenorphine plasma concentrations</description>
    <arm_group_label>Part A Cohort</arm_group_label>
    <arm_group_label>Part B Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Urine sample collection</intervention_name>
    <description>Urine sample for determination of free buprenorphine and free norbuprenorphine concentrations, qualitative UDS for opioids, quantitative UDS for buprenorphine, norbuprenorphine and naloxone, and determination of creatinine concentration</description>
    <arm_group_label>Part A Cohort</arm_group_label>
    <arm_group_label>Part B Cohort</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      PK plasma samples to assess buprenorphine concentrations&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects who participated in either of the studies listed above and who received their last&#xD;
        SUBLOCADE injection within 12 to 30 months of the Screening visit. A maximum of 30 subjects&#xD;
        may continue to Part B and will return for 2 additional visits 30 days apart.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participated in Study RB-US-13-0003 or both Studies RB-US-13-0003 and INDV-6000-301&#xD;
             and received at least 2 subcutaneous (SC) injections of SUBLOCADE&#xD;
&#xD;
          -  Within 12 to 36 months post his or her last SUBLOCADE injection at the time of the&#xD;
             Screening Visit&#xD;
&#xD;
          -  Female individuals of childbearing potential must agree to have a pregnancy test&#xD;
             administered prior to enrollment and throughout the study. Pregnancy does not prohibit&#xD;
             participation&#xD;
&#xD;
          -  Willing to adhere to study procedures and provide written informed consent prior to&#xD;
             the start of any study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received SUBLOCADE or any other long-acting buprenorphine product at any time after&#xD;
             ending their participation in Study RB-US-13-0003 or Study INDV-6000-301&#xD;
&#xD;
          -  Taken any buprenorphine (prescribed or illicit) within 3 weeks prior to the Screening&#xD;
             visit (study Part A, Visit 1)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pathway Healthcare</name>
      <address>
        <city>Hamilton</city>
        <state>Alabama</state>
        <zip>35570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridian Research</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Phoenix Medical Research</name>
      <address>
        <city>Prairie Village</city>
        <state>Kansas</state>
        <zip>66208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adams Clinical</name>
      <address>
        <city>Watertown</city>
        <state>Massachusetts</state>
        <zip>02472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hassman Research Institute</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurobehavioral Clinical Research</name>
      <address>
        <city>North Canton</city>
        <state>Ohio</state>
        <zip>44720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pahl Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SP Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CODA</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Associates of Central PA, LLC</name>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <zip>16602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pillar Research</name>
      <address>
        <city>Richardson</city>
        <state>Texas</state>
        <zip>75080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <results_first_submitted>July 17, 2020</results_first_submitted>
  <results_first_submitted_qc>July 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 3, 2020</results_first_posted>
  <last_update_submitted>August 13, 2020</last_update_submitted>
  <last_update_submitted_qc>August 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2020</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03752528/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>May 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03752528/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>All investigators sites were in the U.S.</recruitment_details>
      <pre_assignment_details>54 subjects were screened. One did not meet eligibility criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <description>All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="53"/>
          </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="43.0" spread="11.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>18 - 44 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>45 - 64 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>.&gt;= 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </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="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79.7" spread="18.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.5" spread="5.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index Group</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt; 18.5 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 18.5 and &lt; 25 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 25 and &lt; 30 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 30 kg/m^2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B</title>
        <description>The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
        <time_frame>Days 1, 30, 60</time_frame>
        <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Cohort: Visit 1</title>
            <description>Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.</description>
          </group>
          <group group_id="O2">
            <title>Part B Cohort: Visit 1</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O3">
            <title>Part B Cohort: Visit 2</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O4">
            <title>Part B Cohort: Visit 3</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B</title>
          <description>The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
          <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</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="49"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Positive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="16"/>
                    <measurement group_id="O4" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Negative</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B</title>
        <description>The quantitative UDS measures both buprenorphine and its glucuronide, or both norbuprenorphine and its glucuronide, with an LLOQ of 2 ng/mL. It is typically used by physicians for the confirmation of a positive result on the qualitative UDS.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
        <time_frame>Days 1, 30, 60</time_frame>
        <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Cohort: Visit 1</title>
            <description>Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.</description>
          </group>
          <group group_id="O2">
            <title>Part B Cohort: Visit 1</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O3">
            <title>Part B Cohort: Visit 2</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O4">
            <title>Part B Cohort: Visit 3</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B</title>
          <description>The quantitative UDS measures both buprenorphine and its glucuronide, or both norbuprenorphine and its glucuronide, with an LLOQ of 2 ng/mL. It is typically used by physicians for the confirmation of a positive result on the qualitative UDS.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
          <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</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="49"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Buprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="23"/>
                    <measurement group_id="O3" value="19"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="19"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine- Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</title>
        <description>The urine free drug test only measures the &quot;free&quot; buprenorphine and &quot;free&quot; norbuprenorphine (without their glucuronides) with an LLOQ of 0.02 ng/mL.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
        <time_frame>Days 1, 30, 60</time_frame>
        <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Cohort: Visit 1</title>
            <description>Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.</description>
          </group>
          <group group_id="O2">
            <title>Part B Cohort: Visit 1</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O3">
            <title>Part B Cohort: Visit 2</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O4">
            <title>Part B Cohort: Visit 3</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</title>
          <description>The urine free drug test only measures the &quot;free&quot; buprenorphine and &quot;free&quot; norbuprenorphine (without their glucuronides) with an LLOQ of 0.02 ng/mL.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
          <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</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="49"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Buprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="17"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine- Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</title>
        <description>A sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was used to assess the plasma exposure to buprenorphine and norbuprenorphine, its major metabolite. The LLOQ was 0.02 ng/mL for both analytes, which is much lower than the LLOQ of plasma/serum assays conducted by diagnostic laboratories.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
        <time_frame>Days 1, 30, 60</time_frame>
        <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Cohort: Visit 1</title>
            <description>Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.</description>
          </group>
          <group group_id="O2">
            <title>Part B Cohort: Visit 1</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O3">
            <title>Part B Cohort: Visit 2</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.</description>
          </group>
          <group group_id="O4">
            <title>Part B Cohort: Visit 3</title>
            <description>Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B</title>
          <description>A sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was used to assess the plasma exposure to buprenorphine and norbuprenorphine, its major metabolite. The LLOQ was 0.02 ng/mL for both analytes, which is much lower than the LLOQ of plasma/serum assays conducted by diagnostic laboratories.&#xD;
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).&#xD;
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is &quot;Not Available&quot;&#xD;
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.</description>
          <population>Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.</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="49"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Buprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Buprenorphine - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norbuprenorphine- Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bup + Nor - Not Available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 to Day 60</time_frame>
      <desc>Only adverse events (AEs) associated with study assessments and/or study conduct were collected.&#xD;
Since there is no study drug for this study, no treatment emergent AE is defined for this study.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Study Participants</title>
          <description>All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.</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="53"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="53"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="53"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Director, Clinical Development</name_or_title>
      <organization>Indivior, Inc.</organization>
      <phone>804-379-1090</phone>
      <email>Robert.Dobbins@Indivior.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03752528
org study id: INDV-6000-402
nct id: NCT03752528
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study objective is to characterise the long-term plasma exposure to buprenorphine after
      stopping SUBLOCADE treatment. There are no interventions planned.

      This multicentre investigation will enroll participants from Study RB-US-13-0003
      (NCT02510014) or both Studies RB-US-13-0003 and INDV-6000-301 (NCT02896296) and who received
      at least 2 subcutaneous (SC) injections of SUBLOCADE.

      There are two parts to the study:

      Part A consists of a single visit during which urine samples are collected to measure free
      buprenorphine and free norbuprenorphine concentrations; qualitative urine drug samples (UDS)
      for opioids, including buprenorphine; quantitative UDS for buprenorphine, norbuprenorphine
      and naloxone; and determination of creatinine concentration. Blood samples are collected for
      the determination of buprenorphine and norbuprenorphine plasma concentrations.

      Results on the quantitative UDS performed in Part A determine enrollment in Part B:
      participants who provide a quantifiable (i.e., positive) result for buprenorphine and/or
      norbuprenorphine and a non-quantifiable (i.e., negative) result for naloxone meet
      continuation criteria to move on to Part B if Part B is still open to enrolment. Part B
      consists of two visits 30 days apart in which the same tests are run as were done in Part A.
Data indicate that after discontinuing SUBLOCADE patients may have detectable concentrations
      of buprenorphine in plasma and urine for 12 months or longer. Previous Phase II/III studies
      did not evaluate the pharmacokinetics (PK) of buprenorphine beyond 2 months after the last
      injection; this study will characterize the long-term plasma exposure starting at least 12
      months after the last injection. The study will also assess relationships between plasma drug
      concentrations, free drug concentrations in urine and urine drug screen (UDS) results in
      order to provide refined guidance to patients and physicians with respect to long-term
      exposure to buprenorphine after stopping SUBLOCADE treatment.
observational model: Case-Only
time perspective: Prospective
measure: Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B
time frame: Days 1, 30, 60
description: The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
measure: Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
time frame: Days 1, 30, 60
description: The quantitative UDS measures both buprenorphine and its glucuronide, or both norbuprenorphine and its glucuronide, with an LLOQ of 2 ng/mL. It is typically used by physicians for the confirmation of a positive result on the qualitative UDS.
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available"
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
measure: Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
time frame: Days 1, 30, 60
description: The urine free drug test only measures the "free" buprenorphine and "free" norbuprenorphine (without their glucuronides) with an LLOQ of 0.02 ng/mL.
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available"
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
measure: Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
time frame: Days 1, 30, 60
description: A sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was used to assess the plasma exposure to buprenorphine and norbuprenorphine, its major metabolite. The LLOQ was 0.02 ng/mL for both analytes, which is much lower than the LLOQ of plasma/serum assays conducted by diagnostic laboratories.
Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3).
For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available"
Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
arm group label: Part A Cohort
description: Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.
arm group label: Part B Cohort
description: Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Visits 2 and 3) which are conducted approximately 30 days apart during which blood and urine samples are collected.
intervention type: Diagnostic Test
intervention name: Blood sample collection
description: Determination of buprenorphine and norbuprenorphine plasma concentrations
arm group label: Part A Cohort
arm group label: Part B Cohort
intervention type: Diagnostic Test
intervention name: Urine sample collection
description: Urine sample for determination of free buprenorphine and free norbuprenorphine concentrations, qualitative UDS for opioids, quantitative UDS for buprenorphine, norbuprenorphine and naloxone, and determination of creatinine concentration
arm group label: Part A Cohort
arm group label: Part B Cohort
PK plasma samples to assess buprenorphine concentrations
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 