<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/NCT01709747</url>
  </required_header>
  <id_info>
    <org_study_id>CNS-HYD202US</org_study_id>
    <nct_id>NCT01709747</nct_id>
  </id_info>
  <brief_title>Single-arm Study to Assess the Safety of Hydromorphone Hydrochloride by Intrathecal Administration</brief_title>
  <official_title>A Phase 3, Open-Label, Single-Arm Study To Assess The Safety Of Hydromorphone Hydrochloride Delivered By Intrathecal Administration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Piramal Critical Care, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Piramal Critical Care, Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the long-term safety of hydromorphone hydrochloride&#xD;
      administered by intrathecal delivery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single-arm safety study to evaluate the safety of hydromorphone&#xD;
      hydrochloride given by continuous intrathecal infusion using an implantable pump device. This&#xD;
      study will enroll both subjects on a current opioid intrathecal medication as well as naïve&#xD;
      subjects now current on intrathecal opioid medications. All subjects currently on intrathecal&#xD;
      opioid treatment will be converted from their current intrathecal therapy to intrathecal&#xD;
      hydromorphone hydrochloride according to standard medical practice. After an optimal dose for&#xD;
      pain relief is achieved, subjects will remain on therapy for a total of 12 months or until&#xD;
      discontinuation from the study. During this continuous dosing period, dose adjustments (up or&#xD;
      down) are permitted to manage pain or side effects provided a maximum dose of 10 mg/day is&#xD;
      not exceeded. Subjects will be assessed for pain intensity using a visual analog scale of&#xD;
      pain intensity (VASPI) instrument at each study visit.&#xD;
&#xD;
      Subjects will be evaluated for side effects and clinical complications associated with the&#xD;
      use of intrathecal hydromorphone. Events will be classified by intrathecal drugs used and&#xD;
      concentrations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2013</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">February 2018</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Granulomas</measure>
    <time_frame>12 months</time_frame>
    <description>Subjects with Clinical Signs and Symptoms of Granuloma [Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI) - Mean Pain Severity</measure>
    <time_frame>Early Termination/Final Visit through 12 months</time_frame>
    <description>Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC)</measure>
    <time_frame>Early Termination/Final Visit through 12 months</time_frame>
    <description>Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analog Scale Pain Intensity (VASPI)</measure>
    <time_frame>Early Termination/Final Visit through 12 months</time_frame>
    <description>Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">364</enrollment>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Hydromorphone Hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hydromorphone hydrochloride for intrathecal administration, 12 months safety evaluation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydromorphone Hydrochloride</intervention_name>
    <description>Opioid for chronic pain</description>
    <arm_group_label>Hydromorphone Hydrochloride</arm_group_label>
    <other_name>Hydromorphone</other_name>
    <other_name>Opioid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Programmable Implantable pump</intervention_name>
    <description>Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
    <arm_group_label>Hydromorphone Hydrochloride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all of the following criteria to be included:&#xD;
&#xD;
          1. Subjects must be at least 18 years of age and no more than 75 years old.&#xD;
&#xD;
          2. Clinically diagnosed with severe chronic pain for at least a 6-month period.&#xD;
&#xD;
          3. Subject is reasonably expected to benefit from intrathecal pain medication and has a&#xD;
             programmable implantable intrathecal pump or meets clinical criteria for implantation&#xD;
             of an intrathecal pump per Standard of Care.&#xD;
&#xD;
          4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting&#xD;
             narcotic prescriptions to the study medication prescribed by the investigator.&#xD;
&#xD;
          5. Subject must be cognitively intact and, in the opinion of the investigator, capable of&#xD;
             participation in the trial.&#xD;
&#xD;
          6. Female subjects of child-bearing potential must agree to use a medically acceptable&#xD;
             and effective double-barrier method of birth control.&#xD;
&#xD;
          7. Subjects who can receive an MRI if required by the study protocol.&#xD;
&#xD;
          8. Provides written Ethics Committee approved informed consent.&#xD;
&#xD;
          9. Willing to comply with all study procedures and requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects meeting any of the following criteria will be excluded:&#xD;
&#xD;
          1. Women who are pregnant or breast-feeding.&#xD;
&#xD;
          2. Subject has any known or suspected allergy to hydromorphone hydrochloride or to the&#xD;
             materials of the infusion pump or intrathecal catheter.&#xD;
&#xD;
          3. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or&#xD;
             benzodiazepines, as defined by Diagnostic and Statistical Manual of Mental Disorders,&#xD;
             4th edition (DSM-IV) criteria, within the past year (physical dependence on prescribed&#xD;
             opioid analgesics is allowed but abuse of opioids according to DSM-IV is not&#xD;
             permitted, i.e. opioid addiction for recreational use).&#xD;
&#xD;
          4. Subjects who show signs of active systemic infection.&#xD;
&#xD;
          5. Subjects with a metastatic cancer to the spinal canal or a known central nervous&#xD;
             system contraindication to intrathecal therapy.&#xD;
&#xD;
          6. Subjects have a condition requiring diathermy procedures.&#xD;
&#xD;
          7. Subject has a life expectancy of less than 12 months.&#xD;
&#xD;
          8. Subjects who are unable or unwilling to return to all of the required follow-up&#xD;
             visits.&#xD;
&#xD;
          9. As a result of medical review and physical examination, the Investigator considers the&#xD;
             subject unfit for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Rauck, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Carolinas Pain Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Center for Clinical Research</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>July 19, 2021</results_first_submitted>
  <results_first_submitted_qc>August 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2021</results_first_posted>
  <disposition_first_submitted>April 9, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>April 23, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 30, 2019</disposition_first_posted>
  <last_update_submitted>August 23, 2021</last_update_submitted>
  <last_update_submitted_qc>August 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hydromorphone Hydrochloride</keyword>
  <keyword>Hydromorphone</keyword>
  <keyword>Pain</keyword>
  <keyword>Chronic Pain</keyword>
  <keyword>Implantable Pump</keyword>
  <keyword>Pump</keyword>
  <keyword>Intrathecal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydromorphone</mesh_term>
  </intervention_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>August 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT01709747/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>February 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT01709747/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Protocol states, &quot;Approximately 350 subjects to be enrolled....... Additional subjects may be enrolled as deemed necessary to reach the study completion requirements for subjects on long term intrathecal hydromorphone hydrochloride therapy.&quot;</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Hydromorphone Hydrochloride</title>
          <description>Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="364"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="287"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All Enrolled Subjects</population>
      <group_list>
        <group group_id="B1">
          <title>Hydromorphone Hydrochloride</title>
          <description>Hydromorphone hydrochloride 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="364"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.3" spread="10.3"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="220"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="356"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="338"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multi-racial (no primary race)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="364"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="364"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Brief Pain Inventory (BPI)</title>
          <description>Brief Pain Inventory (BPI): Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Outcome is Mean Pain Severity score is calculated as the arithmetic mean of the Worst, Least, Average and Now severity scores.</description>
          <population>Intent-to-Treat Population with non-missing data</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="358"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.44" spread="1.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Patient Global Impression of Change (PGIC)</title>
          <description>Patient Global Impression of Change (PGIC): Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome.</description>
          <population>Intent-to-Treat (ITT) Population with non-missing values</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="357"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.24" spread="2.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Visual Analog Scale Pain Intensity (VASPI)</title>
          <description>Visual Analog Scale Pain Intensity (VASPI), Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse.</description>
          <population>Intent-to-Treat (ITT) Population with non-missing assessment</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="363"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.16" spread="26.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Granulomas</title>
        <description>Subjects with Clinical Signs and Symptoms of Granuloma [Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.]</description>
        <time_frame>12 months</time_frame>
        <population>All Enrolled Subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride</title>
            <description>Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Granulomas</title>
          <description>Subjects with Clinical Signs and Symptoms of Granuloma [Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.]</description>
          <population>All Enrolled Subjects</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="364"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Subjects with Clinical Signs and Symptoms of Granuloma</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Subjects without Clinical Signs and Symptoms of Granuloma</title>
                  <measurement_list>
                    <measurement group_id="O1" value="352"/>
                  </measurement_list>
                </category>
                <category>
                  <title>MRI Confirms Granuloma</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Investigator Considers Signs and Symptoms to be Caused by Granuloma</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory (BPI) - Mean Pain Severity</title>
        <description>Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.</description>
        <time_frame>Early Termination/Final Visit through 12 months</time_frame>
        <population>ITT (Intent to Treat) with non-missing Baseline and Early Termination/Final Visit assessment for computing change from baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride</title>
            <description>Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory (BPI) - Mean Pain Severity</title>
          <description>Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.</description>
          <population>ITT (Intent to Treat) with non-missing Baseline and Early Termination/Final Visit assessment for computing change from baseline</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="334"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.20" spread="1.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change (PGIC)</title>
        <description>Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.</description>
        <time_frame>Early Termination/Final Visit through 12 months</time_frame>
        <population>ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride</title>
            <description>Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change (PGIC)</title>
          <description>Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.</description>
          <population>ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="337"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.44" spread="2.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Visual Analog Scale Pain Intensity (VASPI)</title>
        <description>Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.</description>
        <time_frame>Early Termination/Final Visit through 12 months</time_frame>
        <population>ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride</title>
            <description>Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Analog Scale Pain Intensity (VASPI)</title>
          <description>Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.</description>
          <population>ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="344"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.41" spread="26.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Hydromorphone Hydrochloride</title>
          <description>Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Device: Programmable Implantable pump&#xD;
Programmable Implantable pump delivering intrathecal hydromorphone</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>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="7" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="71" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Failure Congestive</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Angina Unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Atrial Flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Melas Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Colitis Ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pancreatitis Acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Chronic Fatigue Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Drug Withdrawal Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Systemic Inflammatory Response Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pyelonephritis Acute</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Bronchitis Viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Implant Site Abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Implant Site Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Localised Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Necrotising Fasciitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pneumonia Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Subdural Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Accidental Overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Femur Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Lower Limb Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </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" subjects_affected="3" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Pancreatic Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrospinal Fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Cognitive Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hepatic Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Uraemic Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental Status Changes</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Bipolar Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Panic Attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal Failure Acute</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Cystitis Haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Obstructive Uropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Renal Colic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic Obstructive Pulmonary Disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Acute Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Precancerous Skin Lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Accelerated Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>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="308" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="51" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="364"/>
              </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" subjects_affected="62" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="364"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="364"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="364"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Heather Kapushoc, Sr. Biostatistician</name_or_title>
      <organization>CTI Clinical Trial and Consulting Services</organization>
      <phone>571-315-2574</phone>
      <email>hkapushoc@ctifacts.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/NCT01709747
org study id: CNS-HYD202US
nct id: NCT01709747
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the long-term safety of hydromorphone hydrochloride
      administered by intrathecal delivery.
This is an open-label, single-arm safety study to evaluate the safety of hydromorphone
      hydrochloride given by continuous intrathecal infusion using an implantable pump device. This
      study will enroll both subjects on a current opioid intrathecal medication as well as naïve
      subjects now current on intrathecal opioid medications. All subjects currently on intrathecal
      opioid treatment will be converted from their current intrathecal therapy to intrathecal
      hydromorphone hydrochloride according to standard medical practice. After an optimal dose for
      pain relief is achieved, subjects will remain on therapy for a total of 12 months or until
      discontinuation from the study. During this continuous dosing period, dose adjustments (up or
      down) are permitted to manage pain or side effects provided a maximum dose of 10 mg/day is
      not exceeded. Subjects will be assessed for pain intensity using a visual analog scale of
      pain intensity (VASPI) instrument at each study visit.

      Subjects will be evaluated for side effects and clinical complications associated with the
      use of intrathecal hydromorphone. Events will be classified by intrathecal drugs used and
      concentrations.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Granulomas
time frame: 12 months
description: Subjects with Clinical Signs and Symptoms of Granuloma [Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.]
measure: Brief Pain Inventory (BPI) - Mean Pain Severity
time frame: Early Termination/Final Visit through 12 months
description: Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.
measure: Patient Global Impression of Change (PGIC)
time frame: Early Termination/Final Visit through 12 months
description: Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.
measure: Visual Analog Scale Pain Intensity (VASPI)
time frame: Early Termination/Final Visit through 12 months
description: Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.
arm group label: Hydromorphone Hydrochloride
arm group type: Experimental
description: Hydromorphone hydrochloride for intrathecal administration, 12 months safety evaluation
intervention type: Drug
intervention name: Hydromorphone Hydrochloride
description: Opioid for chronic pain
arm group label: Hydromorphone Hydrochloride
other name: Hydromorphone
other name: Opioid
intervention type: Device
intervention name: Programmable Implantable pump
description: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
arm group label: Hydromorphone Hydrochloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Richard Rauck, MD
role: Principal Investigator
affiliation: Carolinas Pain Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Hydromorphone
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 