<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/NCT03810495</url>
  </required_header>
  <id_info>
    <org_study_id>GM0017</org_study_id>
    <secondary_id>UG3DA047720</secondary_id>
    <secondary_id>240358</secondary_id>
    <nct_id>NCT03810495</nct_id>
  </id_info>
  <brief_title>The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers</brief_title>
  <official_title>OLANI PK/Safety Study in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Go Medical Industries Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinilabs, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Go Medical Industries Pty Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine the pharmacokinetic profile and safety of the O'Neil Long Acting&#xD;
      Naltrexone Implant (OLANI) overtime in healthy volunteers. All participants will be treated&#xD;
      in an open label manner. No randomization will occur. It is hypothesized that the OLANI will&#xD;
      provide sustained therapeutic doses of naltrexone (NTX) for periods up to 6 months via a&#xD;
      single subcutaneous application of 2 OLANIs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Naltrexone (NTX) is a nonspecific pure opioid antagonist with a high affinity for the&#xD;
      µ-opioid receptor. It blocks the effects of opioids by competitive binding at opiate&#xD;
      receptors. NTX is used primarily in the management of opiate and alcohol dependence. It is&#xD;
      available in the United States (US) as 2 formulations; a once daily oral formulation (Revia)&#xD;
      and a once monthly intramuscular injection (Vivitrol). While NTX is a potent antagonist and&#xD;
      efficiently blocks the effects of exogenous opiates such as heroin, the success of NTX for&#xD;
      the treatment of opiate dependence has been limited by poor patient compliance. Therefore,&#xD;
      the development of a sustained release NTX formulation (in excess of 1 month) would be of&#xD;
      great benefit for the treatment of opioid use disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 11, 2019</start_date>
  <completion_date type="Actual">March 22, 2021</completion_date>
  <primary_completion_date type="Actual">March 18, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants That Maintain MEC</measure>
    <time_frame>up to 540 days or until NTX blood levels become undetectable</time_frame>
    <description>Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Cmax of Naltrexone</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of Naltrexone</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Naltrexone</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Cmax of 6β-naltrexol</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Tmax of 6β-naltrexol</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time&gt;Minimum Effective Concentration</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of 6β-naltrexol</measure>
    <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
    <description>Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (AEs)</measure>
    <time_frame>Up to 540 days or until NTX blood levels become undetectable</time_frame>
    <description>Incidence and Severity of AEs</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Opioid Use Disorder</condition>
  <arm_group>
    <arm_group_label>OLANI (naltrexone implant)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>naltrexone implant</intervention_name>
    <description>1.8 g implant containing 60% naltrexone</description>
    <arm_group_label>OLANI (naltrexone implant)</arm_group_label>
    <other_name>OLANI</other_name>
    <other_name>O'Neil Long Acting Naltrexone Implant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women between the ages of 18 and 55 years old (inclusive)&#xD;
&#xD;
          -  Without The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM&#xD;
             5) - Substance Related Disorders classification; in sustained remission is not&#xD;
             exclusionary&#xD;
&#xD;
          -  Able and willing to comply with the requirements of the protocol&#xD;
&#xD;
          -  Able and willing to provide written informed consent&#xD;
&#xD;
          -  Willing to undergo a minor surgical procedure under local anesthetic to allow for&#xD;
             investigational drug administration in the subcutaneous tissue&#xD;
&#xD;
          -  BMI inclusive of 18.5 to 30.0&#xD;
&#xD;
          -  Have an initial weight between 45.3 and 81.6 kilograms (inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive urine drug screen (UDS) at screening for illicit substances.&#xD;
&#xD;
          -  Is currently on naltrexone medication.&#xD;
&#xD;
          -  Has had a naltrexone implant in the past 24 months.&#xD;
&#xD;
          -  Has received treatment with an extended naltrexone product (e.g. Vivitrol) in the past&#xD;
             12 months.&#xD;
&#xD;
          -  Has a condition which requires treatment with opioid based medication.&#xD;
&#xD;
          -  Has a known hypersensitivity to naltrexone.&#xD;
&#xD;
          -  Has a known hypersensitivity to poly-lactic based materials e.g. biodegradable&#xD;
             sutures, surgical implants or previous biodegradable implants.&#xD;
&#xD;
          -  Has a known hypersensitivity to local anesthesia.&#xD;
&#xD;
          -  Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema&#xD;
             that is likely to impact the implant site area, or as determined by the evaluating&#xD;
             physician.&#xD;
&#xD;
          -  Demonstrates any abnormal skin tissue in the proposed implantation area.&#xD;
&#xD;
          -  Is pregnant or planning to be. Women need to have negative blood pregnancy test at&#xD;
             screening. Women need to agree to practice dual contraceptives.&#xD;
&#xD;
          -  Participant is breastfeeding or planning to be.&#xD;
&#xD;
          -  Has a current significant neurological (including cognitive and psychiatric&#xD;
             disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary,&#xD;
             hematological or metabolic disease unless currently controlled and stable with&#xD;
             protocol-allowed medication 30 days prior to proposed investigational product&#xD;
             administration.&#xD;
&#xD;
          -  Any clinically important abnormal finding as determined by medical history, physical&#xD;
             examination, ECG or clinical laboratory tests.&#xD;
&#xD;
          -  Any additional condition(s) that in the investigator's opinion would prohibit the&#xD;
             participant from completing the study or would not be in the best interest of the&#xD;
             participant.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) or aspartate transaminase (AST) &gt; 3 times the upper end&#xD;
             of the laboratory normal range.&#xD;
&#xD;
          -  Any methadone use 14 days prior to screening, and up to Study Day 0.&#xD;
&#xD;
          -  Current DSM-5 diagnosis of schizophrenia, bipolar, anxiety, or depressive disorder,&#xD;
             confirmed by The Mini International Neuropsychiatric Interview (MINI) diagnostic&#xD;
             interview assessment, or currently treated with medications for anxiety or depression.&#xD;
             Past history (in remission DSM-5 classification) of anxiety or depression is not&#xD;
             exclusionary.&#xD;
&#xD;
          -  Any elevated risk for suicide measured using the Columbia Suicide Severity Rating&#xD;
             Scale (C-SSRS), endorsing any of the items in the past month (C-SSRS, Lifetime)&#xD;
&#xD;
          -  Is participating or intending to participate in any other clinical trial during the&#xD;
             duration of this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam Bisaga, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <results_first_submitted>July 6, 2022</results_first_submitted>
  <results_first_submitted_qc>July 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2022</results_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>naltrexone</keyword>
  <keyword>opioids</keyword>
  <keyword>opioid use disorder</keyword>
  <keyword>OLANI implant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>June 11, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03810495/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03810495/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>OLANI (Naltrexone Implant)</title>
          <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </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="2"/>
              </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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>OLANI (Naltrexone Implant)</title>
          <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </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="38.4" spread="10.77"/>
                  </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="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </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 (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="1"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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>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="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (kg/m^2)</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="24.92" spread="3.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants That Maintain MEC</title>
        <description>Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days</description>
        <time_frame>up to 540 days or until NTX blood levels become undetectable</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants That Maintain MEC</title>
          <description>Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Cmax of Naltrexone</title>
        <description>Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Median Cmax of Naltrexone</title>
          <description>Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.00" lower_limit="5.38" upper_limit="71.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax of Naltrexone</title>
        <description>Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax of Naltrexone</title>
          <description>Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>day</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.63" lower_limit="0.47" upper_limit="268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC of Naltrexone</title>
        <description>Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>AUC of Naltrexone</title>
          <description>Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>day*ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1440.5" lower_limit="991.1" upper_limit="2022"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Cmax of 6β-naltrexol</title>
        <description>Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Median Cmax of 6β-naltrexol</title>
          <description>Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.45" lower_limit="10.2" upper_limit="126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Tmax of 6β-naltrexol</title>
        <description>Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Median Tmax of 6β-naltrexol</title>
          <description>Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>day</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.70" lower_limit="1" upper_limit="176.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time&gt;Minimum Effective Concentration</title>
        <description>Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Time&gt;Minimum Effective Concentration</title>
          <description>Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="6" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC of 6β-naltrexol</title>
        <description>Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1</description>
        <time_frame>pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days</time_frame>
        <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>AUC of 6β-naltrexol</title>
          <description>Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1</description>
          <population>Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as &lt;0.1 ng/mL) and those without any major protocol deviations.</population>
          <units>day*ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2856.50" lower_limit="1484" upper_limit="4990"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Events (AEs)</title>
        <description>Incidence and Severity of AEs</description>
        <time_frame>Up to 540 days or until NTX blood levels become undetectable</time_frame>
        <group_list>
          <group group_id="O1">
            <title>OLANI (Naltrexone Implant)</title>
            <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events (AEs)</title>
          <description>Incidence and Severity of AEs</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with at least One Treatment-Emergent Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Implant site inflammation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Implant site pruritus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhoea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Upper respiratory tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Implant site pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Back pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>OLANI (Naltrexone Implant)</title>
          <description>2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously&#xD;
naltrexone implant: 1.8 g implant containing 60% naltrexone</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <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="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>Cannabinoid hyperemesis syndrome</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Stab Wound</sub_title>
                <description>Multiple severe stab wounds to the iliac crest, mid-thorax and shoulder blade</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Implant site inflammation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Implant site pruritus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Implant site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Implant site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bacterial vaginosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Corona virus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Clavicle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eyelid injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Stab wound</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Exploratory operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This is a pilot study with a small sample size.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Director of Operations</name_or_title>
      <organization>Go Medical Industries, Pty Ltd</organization>
      <phone>61(8) 9388 1700</phone>
      <email>ctc@gomedical.com.au</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/NCT03810495
org study id: GM0017
secondary id: UG3DA047720
secondary id: 240358
nct id: NCT03810495
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will examine the pharmacokinetic profile and safety of the O'Neil Long Acting
      Naltrexone Implant (OLANI) overtime in healthy volunteers. All participants will be treated
      in an open label manner. No randomization will occur. It is hypothesized that the OLANI will
      provide sustained therapeutic doses of naltrexone (NTX) for periods up to 6 months via a
      single subcutaneous application of 2 OLANIs.
Naltrexone (NTX) is a nonspecific pure opioid antagonist with a high affinity for the
      µ-opioid receptor. It blocks the effects of opioids by competitive binding at opiate
      receptors. NTX is used primarily in the management of opiate and alcohol dependence. It is
      available in the United States (US) as 2 formulations; a once daily oral formulation (Revia)
      and a once monthly intramuscular injection (Vivitrol). While NTX is a potent antagonist and
      efficiently blocks the effects of exogenous opiates such as heroin, the success of NTX for
      the treatment of opiate dependence has been limited by poor patient compliance. Therefore,
      the development of a sustained release NTX formulation (in excess of 1 month) would be of
      great benefit for the treatment of opioid use disorder.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Percentage of Participants That Maintain MEC
time frame: up to 540 days or until NTX blood levels become undetectable
description: Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days
measure: Median Cmax of Naltrexone
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1
measure: Tmax of Naltrexone
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1
measure: AUC of Naltrexone
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1
measure: Median Cmax of 6β-naltrexol
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1
measure: Median Tmax of 6β-naltrexol
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1
measure: Time>Minimum Effective Concentration
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33
measure: AUC of 6β-naltrexol
time frame: pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
description: Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1
measure: Incidence of Adverse Events (AEs)
time frame: Up to 540 days or until NTX blood levels become undetectable
description: Incidence and Severity of AEs
arm group label: OLANI (naltrexone implant)
arm group type: Experimental
description: 2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously
intervention type: Drug
intervention name: naltrexone implant
description: 1.8 g implant containing 60% naltrexone
arm group label: OLANI (naltrexone implant)
other name: OLANI
other name: O'Neil Long Acting Naltrexone Implant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adam Bisaga, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Naltrexone
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This is a pilot study with a small sample size.
point of contact: 