<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/NCT01709721</url>
  </required_header>
  <id_info>
    <org_study_id>CNS-HYD201US</org_study_id>
    <nct_id>NCT01709721</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of Hydromorphone Hydrochloride by Intrathecal Administration</brief_title>
  <official_title>A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a Programmable Implantable Pump</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 determine the safety and efficacy of hydromorphone&#xD;
      hydrochloride by intrathecal administration using a programmable implantable pump.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and&#xD;
      Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a&#xD;
      Programmable Implantable Pump&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period</measure>
    <time_frame>5 weeks [Baseline (Day 84) to Day 119 Visit]</time_frame>
    <description>Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of &gt;= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119.&#xD;
Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period.&#xD;
Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS &gt; 12 during the randomized phase will not be classified as a treatment failure.&#xD;
Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI): Pain Severity, &quot;Worst&quot;</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119 Visit]</time_frame>
    <description>'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI): Pain Severity &quot;Average&quot;</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI): Pain Severity Summary Measure</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory: Interference With Function Summary Measure</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Rescue Medication After Randomization (Days)</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC)</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure]</time_frame>
    <description>The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Opioid Supplement Consumption</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Rescue - Rescue Medication Given</measure>
    <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
    <description>Number of subjects with rescue medication given</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Management of Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Hydromorphone Hydrochloride (Randomized/Double-Blind)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects on hydromorphone hydrochloride for the duration of therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects on hydromorphone hydrochloride titrated downward</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 (Randomized/Double-Blind)</arm_group_label>
    <arm_group_label>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</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>Programmable Implantable pump delivering intrathecal hydromorphone</description>
    <arm_group_label>Hydromorphone Hydrochloride (Randomized/Double-Blind)</arm_group_label>
    <arm_group_label>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</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. Subject must be at least 18 years of age and no more than 75 years old.&#xD;
&#xD;
          2. Clinically diagnosed with chronic pain for at least a 6-month period.&#xD;
&#xD;
          3. Subject is presently on intrathecal pain medication and has a SynchroMed II&#xD;
             Implantable pump or meets clinical criteria for implantation of a SynchroMed II&#xD;
             Implantable pump. Subjects who are naïve to intrathecal therapy, may be enrolled&#xD;
             2-weeks after pump implantation.&#xD;
&#xD;
          4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting&#xD;
             narcotic prescriptions to the study physician.&#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 with existing SynchroMed II Implantable pumps and are reasonably expected to&#xD;
             benefit from intrathecal opioid therapy only.&#xD;
&#xD;
          8. Subjects who are capable of receiving an MRI with or without contrast or CT myelogram,&#xD;
             if required by the study protocol.&#xD;
&#xD;
          9. Provides written Ethics Committee approved informed consent.&#xD;
&#xD;
         10. 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 are breast-feeding&#xD;
&#xD;
          2. Subjects who have participated in an investigational drug or device trial within 4&#xD;
             weeks prior to enrollment.&#xD;
&#xD;
          3. Subject has any known or suspected allergy to hydromorphone or to the materials of the&#xD;
             infusion pump or intrathecal catheter.&#xD;
&#xD;
          4. Subject is scheduled for a pump or catheter replacement within 6 months of their&#xD;
             enrollment into the trial.&#xD;
&#xD;
          5. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or&#xD;
             benzodiazepines, as defined by DSM-IV criteria, within the past year (physical&#xD;
             dependence on prescribed opioid analgesics is allowed but abuse of opioids according&#xD;
             to DSM-IV is not permitted, i.e. opioid addiction for recreational use).&#xD;
&#xD;
          6. Subjects who show signs of active systemic infection.&#xD;
&#xD;
          7. Subjects with a metastatic cancer to the spinal canal or a known central nervous&#xD;
             system contraindication to intrathecal therapy.&#xD;
&#xD;
          8. Subject has a condition requiring diathermy procedures.&#xD;
&#xD;
          9. Subject has a life expectancy of less than 12 months.&#xD;
&#xD;
         10. Subject cannot independently comprehend and participate in the required assessments,&#xD;
             including responding to the VASPI, Short-form McGill Pain Questionnaire (SF-MPQ),&#xD;
             Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS),&#xD;
             BPI and patient global impression of change (PGIC) measurement tools.&#xD;
&#xD;
         11. Subject is not considered to be medically or psychologically appropriate for pump&#xD;
             implantation.&#xD;
&#xD;
         12. Subjects who are unable or unwilling to return to all of the required follow-up&#xD;
             visits.&#xD;
&#xD;
         13. Subjects with active implanted devices such as pacemakers, defibrillators, and&#xD;
             cochlear implants or other medical device use, if in the opinion of the investigator&#xD;
             the device would interfere with the ability to perform an MRI or CT myelogram.&#xD;
&#xD;
         14. As a result of medical review and physical examination, the Investigator considers the&#xD;
             subject unfit for the study.&#xD;
&#xD;
         15. Pain located above the shoulders in the head or neck region (e.g. trigeminal&#xD;
             neuralgia), central pain syndromes or any other condition in which it is judged to be&#xD;
             unlikely that the subject would benefit from intrathecal administration of the drug&#xD;
             product.&#xD;
&#xD;
         16. Subjects who have previously been unresponsive to intrathecal hydromorphone therapy.&#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 L Rauck, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Center for Clinical Research</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>October 2021</verification_date>
  <study_first_submitted>August 24, 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 22, 2021</results_first_submitted>
  <results_first_submitted_qc>July 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2021</results_first_posted>
  <disposition_first_submitted>April 24, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>April 24, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 30, 2019</disposition_first_posted>
  <last_update_submitted>October 12, 2021</last_update_submitted>
  <last_update_submitted_qc>October 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hydromorphone</keyword>
  <keyword>Hydromorphone Hydrochloride</keyword>
  <keyword>Pain Management</keyword>
  <keyword>Non-narcotic analgesics</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/21/NCT01709721/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/21/NCT01709721/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
          <description>Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
        <group group_id="P2">
          <title>Hydromorphone Titrated Downward/Control (Randomized/Double-Blind)</title>
          <description>Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
        <group group_id="P3">
          <title>Not Randomized (Open Label Only)</title>
          <description>Enrolled but Not Randomized, dropped out during Open Label phase. Open Label treatment only of their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Open Label Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="72"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="72"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance With Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Changes In The Subject's Condition Render The Subject Unacceptable For Further Treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Inadequate Pain Control</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="37"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other, Specify in text field in database</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Randomized Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Inadequate Pain Control</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other, Specify text field in database</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All Enrolled Subjects</population>
      <group_list>
        <group group_id="B1">
          <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
          <description>Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
        </group>
        <group group_id="B2">
          <title>Hydromorphone Titrated Downward/Control (Randomized/Double-Blind)</title>
          <description>Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump</description>
        </group>
        <group group_id="B3">
          <title>Not Randomized (Open Label Only)</title>
          <description>Enrolled but Not Randomized, dropped out during Open Label phase. Open Label treatment only of their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="41"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="72"/>
            <count group_id="B4" value="153"/>
          </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="53.6" spread="11.5"/>
                    <measurement group_id="B2" value="54.8" spread="8.3"/>
                    <measurement group_id="B3" value="57.1" spread="9.7"/>
                    <measurement group_id="B4" value="55.6" spread="10"/>
                  </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="27"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="61"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="69"/>
                    <measurement group_id="B4" value="147"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" 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 group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="144"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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="41"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="72"/>
                    <measurement group_id="B4" value="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period</title>
        <description>Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of &gt;= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119.&#xD;
Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period.&#xD;
Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS &gt; 12 during the randomized phase will not be classified as a treatment failure.&#xD;
Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.</description>
        <time_frame>5 weeks [Baseline (Day 84) to Day 119 Visit]</time_frame>
        <population>Intent-to-Treat - Randomized Subjects. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period</title>
          <description>Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of &gt;= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119.&#xD;
Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period.&#xD;
Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS &gt; 12 during the randomized phase will not be classified as a treatment failure.&#xD;
Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.</description>
          <population>Intent-to-Treat - Randomized Subjects. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</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="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Superiority of intrathecal hydromorphone hydrochloride as compared to a control arm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.147</p_value>
            <method>Chi-squared</method>
            <method_desc>Pearson's chi-square test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory (BPI): Pain Severity, &quot;Worst&quot;</title>
        <description>'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119 Visit]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory (BPI): Pain Severity, &quot;Worst&quot;</title>
          <description>'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.62" spread="0.42"/>
                    <measurement group_id="O2" value="6.62" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.&#xD;
Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).&#xD;
Note: Baseline for this analysis is the Day 84 visit.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0342</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory (BPI): Pain Severity &quot;Average&quot;</title>
        <description>'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory (BPI): Pain Severity &quot;Average&quot;</title>
          <description>'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.09" spread="0.34"/>
                    <measurement group_id="O2" value="4.78" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.&#xD;
Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).&#xD;
Note: Baseline for this analysis is the Day 84 visit.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1642</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory (BPI): Pain Severity Summary Measure</title>
        <description>Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory (BPI): Pain Severity Summary Measure</title>
          <description>Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score on scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.19" spread="0.35"/>
                    <measurement group_id="O2" value="5.24" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.&#xD;
Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).&#xD;
Note: Baseline for this analysis is the Day 84 visit.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0160</p_value>
            <method>ANCOVA</method>
            <method_desc>ANCOVA, with randomization group as the factor and initial parameter value as covariate.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory: Interference With Function Summary Measure</title>
        <description>Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory: Interference With Function Summary Measure</title>
          <description>Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score on scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.76" spread="0.44"/>
                    <measurement group_id="O2" value="5.54" spread="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.&#xD;
Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).&#xD;
Note: Baseline for this analysis is the Day 84 visit.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0007</p_value>
            <method>ANCOVA</method>
            <method_desc>ANCOVA, with randomization group as the factor and initial parameter value as covariate.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score</title>
        <description>The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score</title>
          <description>The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score on a scale, summed across 15 quest</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.05" spread="1.53"/>
                    <measurement group_id="O2" value="16.95" spread="1.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.&#xD;
Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).&#xD;
Note: Baseline for this analysis is the Day 84 visit.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0088</p_value>
            <p_value_desc>ANCOVA, with randomization group as the factor and initial parameter value as covariate.</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Rescue Medication After Randomization (Days)</title>
        <description>The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Rescue Medication After Randomization (Days)</title>
          <description>The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.85" spread="6.32"/>
                    <measurement group_id="O2" value="24.35" spread="9.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.011</p_value>
            <p_value_desc>Log-rank test for Kaplan-Meier Estimate of Time to Rescue (days).</p_value_desc>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change (PGIC)</title>
        <description>The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change (PGIC)</title>
          <description>The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>score 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="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.95" spread="1.70"/>
                    <measurement group_id="O2" value="3.73" spread="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value by the Cochran-Mantel-Haenszel mean score test (using equally spaced scores).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0335</p_value>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Opioid Supplement Consumption</title>
        <description>Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Opioid Supplement Consumption</title>
          <description>Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
          <units>milligrams (mg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6916.88" spread="14102.91"/>
                    <measurement group_id="O2" value="1732.84" spread="5984.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Rescue - Rescue Medication Given</title>
        <description>Number of subjects with rescue medication given</description>
        <time_frame>5 Weeks [Baseline (Day 84) to Day 119]</time_frame>
        <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
            <description>Subjects on hydromorphone hydrochloride for the duration of therapy.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
          <group group_id="O2">
            <title>Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)</title>
            <description>Hydromorphone Hydrochloride/Control Titrated Downward&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Rescue - Rescue Medication Given</title>
          <description>Number of subjects with rescue medication given</description>
          <population>Intent-to-Treat - Randomized. Subjects in the Open Label Phase of the study who discontinued the study prior to the Randomization Phase and/or did not meet the criteria for randomization are not included in this analysis as they were not randomized to a treatment group.</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="41"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Pearson's chi-square test</non_inferiority_desc>
            <p_value>0.010</p_value>
            <p_value_desc>Pearson's chi-square test</p_value_desc>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 Weeks</time_frame>
      <desc>Includes all subjects who have study medication loaded into their intrathecal pump (ie, any exposure to hydromorphone hydrochloride).</desc>
      <group_list>
        <group group_id="E1">
          <title>Hydromorphone Hydrochloride (Randomized/Double-Blind)</title>
          <description>Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
        <group group_id="E2">
          <title>Hydromorphone Titrated Downward/Control (Randomized/Double-Blind)</title>
          <description>Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump&#xD;
Hydromorphone Hydrochloride: Opioid for chronic pain&#xD;
Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride</description>
        </group>
        <group group_id="E3">
          <title>Not Randomized (Open Label Only)</title>
          <description>Enrolled but not randomized [Entered Open Label Phase includes visits from Day 1 until date of randomization (Day 84)]</description>
        </group>
        <group group_id="E4">
          <title>All Subjects</title>
          <description>Total serious adverse events from Day 1 through end of study</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (12.1)</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="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina Unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oesophageal Achalasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Withdrawal Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Drug Intolerance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Clostridium Difficile Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Implant Site Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Implant Site Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Incision Site Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Cervical Vertebral Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Seroma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Basal Ganglia Stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (12.1)</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="35" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="56" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="127" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="35" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Withdrawal Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="22" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Joint Injury</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Thermal Burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </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="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Sacroiliitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="153"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="153"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="153"/>
              </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/NCT01709721
org study id: CNS-HYD201US
nct id: NCT01709721
lead sponsor: 
has dmc: No
The purpose of this study is to determine the safety and efficacy of hydromorphone
      hydrochloride by intrathecal administration using a programmable implantable pump.
A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and
      Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a
      Programmable Implantable Pump
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
measure: Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period
time frame: 5 weeks [Baseline (Day 84) to Day 119 Visit]
description: Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of >= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119.
Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period.
Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS > 12 during the randomized phase will not be classified as a treatment failure.
Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.
measure: Brief Pain Inventory (BPI): Pain Severity, "Worst"
time frame: 5 Weeks [Baseline (Day 84) to Day 119 Visit]
description: 'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.
measure: Brief Pain Inventory (BPI): Pain Severity "Average"
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: 'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.
measure: Brief Pain Inventory (BPI): Pain Severity Summary Measure
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.
measure: Brief Pain Inventory: Interference With Function Summary Measure
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.
measure: Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.
measure: Time to Rescue Medication After Randomization (Days)
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.
measure: Patient Global Impression of Change (PGIC)
time frame: 5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure]
description: The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.
measure: Oral Opioid Supplement Consumption
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.
measure: Time to Rescue - Rescue Medication Given
time frame: 5 Weeks [Baseline (Day 84) to Day 119]
description: Number of subjects with rescue medication given
arm group label: Hydromorphone Hydrochloride (Randomized/Double-Blind)
arm group type: Experimental
description: Subjects on hydromorphone hydrochloride for the duration of therapy.
arm group label: Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
arm group type: Active Comparator
description: Subjects on hydromorphone hydrochloride titrated downward
intervention type: Drug
intervention name: Hydromorphone Hydrochloride
description: Opioid for chronic pain
arm group label: Hydromorphone Hydrochloride (Randomized/Double-Blind)
arm group label: Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
other name: Hydromorphone
other name: Opioid
intervention type: Device
intervention name: Programmable Implantable pump
description: Programmable Implantable pump delivering intrathecal hydromorphone
arm group label: Hydromorphone Hydrochloride (Randomized/Double-Blind)
arm group label: Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Richard L Rauck, MD
role: Principal Investigator
affiliation: The Center for Clinical Research
facility: 
country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Hydromorphone
sharing ipd: No
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 