<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/NCT01675531</url>
  </required_header>
  <id_info>
    <org_study_id>OXN12-KR-402</org_study_id>
    <nct_id>NCT01675531</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Efficacy and Safety of Oxycodone/Naloxone in Korean Patients With Chemotherapy-Induced Peripheral Neuropathy (CIPN)</brief_title>
  <official_title>A Multicenter, Phase IV, Interventional Study to Assess the Efficacy and Safety of Oxycodone/Naloxone in Korean Patients With Chemotherapy-Induced Peripheral Neuropathy Who Need Opioid Combination Treatment With Existing Pregabalin Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mundipharma Korea Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mundipharma Korea Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multicenter, phase IV, interventional study to assess the efficacy and safety of Targin&#xD;
      (Oxycodone/Naloxone) Korean patients with CIPN (Chemotherapy-Induced Peripheral Neuropathy)&#xD;
      who need opioid combination treatment with existing pregabalin of last dose prior to study&#xD;
      enrollment without changing.&#xD;
&#xD;
      The investigators will assess study objectives as below.&#xD;
&#xD;
      Primary objective&#xD;
&#xD;
        -  To assess the pain reduction rate after 4 weeks treatment from baseline (week 0)&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
        -  To assess the Functional Assessment of Cancer Therapy/Gynecologic Oncology&#xD;
           Group-Neurotoxicity (FACIT-GOG/NTX)&#xD;
&#xD;
        -  To assess physician's overall satisfaction&#xD;
&#xD;
        -  To assess subject's overall satisfaction&#xD;
&#xD;
        -  To assess safety&#xD;
&#xD;
      The investigators have a hypothesis that Targin will show favorable efficacy &amp; safety profile&#xD;
      for CIPN patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a multicenter, phase IV, interventional study to assess the efficacy and safety&#xD;
      of Targin (Oxycodone/Naloxone) Korean patients with CIPN(Chemotherapy-Induced Peripheral&#xD;
      Neuropathy) who need opioid combination treatment with existing pregabalin of last dose prior&#xD;
      to study enrollment without changing.&#xD;
&#xD;
      Upon providing written informed consent, subject will be screened in the study and assessment&#xD;
      will be performed at that time such as safety data (adverse event (AE)/serious adverse events&#xD;
      (SAEs)) including laboratory results, physical examination, vital sign, medical history&#xD;
      taking, 24 hours pain intensity score, Functional Assessment of Cancer Therapy/Gynecologic&#xD;
      Oncology Group-Neurotoxicity (FACT-GOG/NTX), physician's overall satisfaction and subject's&#xD;
      overall satisfaction. If patient is eligible in inclusion/exclusion criteria at the time of&#xD;
      visit 1, the patient will receive treatment with Targin. Re-screening, study drug dose&#xD;
      interruption is not allowed. The duration of study drug dose interruption is defined as for 1&#xD;
      week.&#xD;
&#xD;
      Treatment with Targin will be started at 10/5mg twice daily for 4 weeks, and proper titration&#xD;
      (up-titration) will be allowed at each visit according to the investigator's decision. Dose&#xD;
      titration up to a maximum of Targin 40/20mg twice daily will be permitted during study&#xD;
      period.&#xD;
&#xD;
      The up-titration will be considered by investigator's judgement as followings; (1) if the&#xD;
      rescue medication was used more than 2 times per day, on average or (2) based on the daily&#xD;
      average Numeric Rating Scale (NRS), if the NRS was changed to worsen since the previous&#xD;
      visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose,&#xD;
      frequency of rescue medication).&#xD;
&#xD;
      Safety laboratories will be obtained at baseline (visit 1) and study end (visit 4) in a local&#xD;
      laboratory. The laboratory values within 4 weeks prior to baseline (visit 1) will be allowed&#xD;
      to use at study visit 1.&#xD;
&#xD;
      The rescue medication is the 5mg of (Immediate release codon trade mark)IRcodonTM .&#xD;
&#xD;
      Patients will be withdrawn from the study if the following circumstance require study drug&#xD;
      discontinuation:&#xD;
&#xD;
      Failure of pain control (Failure of pain control will be decided by investigators judgement,&#xD;
      e.g. there is poor pain control or lack of efficacy despite 2~3 times of up titration.)&#xD;
      Adjustment of the other analgesics due to AEs except Targin or IRcodonTM Adjustment of the&#xD;
      other major pain management modality (e.g. chemotherapy, radiotherapy, surgery, non-surgical&#xD;
      interventional therapy, etc.) Withdrawal of informed consent Pregnancy Any other significant&#xD;
      risk to the patient's safety in the clinical judgement of the investigator&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>NRS (Numeric Rating Scale)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Change of pain intensity score via NRS after vist 4 weeks treatment from baseline (week 0).&#xD;
NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week4/ET minus mean score at Baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in FACT-GOG/NTX From Visit1(Week 0) to Visit 4(Week 4 Post-treatment).</measure>
    <time_frame>4 weeks</time_frame>
    <description>Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FAICT-GOG/NTX).&#xD;
The mean changes in FACT/GOG-NTX total score and each FACT/GOG-NTX subscale score from Visit 1 (Week 0) to Visit 4 (Week 4 post-treatment) were analyzed. Missing data was handled as LOCF(Last Observation Carried Forward Method).&#xD;
FACT/GOG-NTX total score range was from 0 to 152. The average change score from baseline to visit 4 indicates thay a lower score on the FACT/GOG-NTX means lower quality of life and a greater impact of neurotoxic symptom on the patient's life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physician's Overall Satisfaction</measure>
    <time_frame>4 weeks</time_frame>
    <description>Physician's overall satisfaction was scored 7 scales from Very much worse to Very much improved. (Very much worse, much worse, minimally worse, No change, Minimally improved, much improved, very much improved).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Overall Satisfaction</measure>
    <time_frame>4weeks</time_frame>
    <description>Patient's overall satisfaction was assessed 7 scales from very much worse to very much improved. (Very much worse, much worse, minimally worse, no change, minimally improved, much improved, very much improved)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Targin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Targin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Targin</intervention_name>
    <description>Single arm for Targin</description>
    <arm_group_label>Targin</arm_group_label>
    <other_name>Oxycodone and Naloxone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female ≥ 20 and &lt;80 years of age&#xD;
&#xD;
          -  Patients who has diagnosed as Chemotherapy-Induced Peripheral Neuropathy by&#xD;
             investigator's judgment&#xD;
&#xD;
          -  Patient who are receiving pregabalin for the treatment of Chemotherapy- Induced&#xD;
             Peripheral Neuropathy&#xD;
&#xD;
          -  Patients who have moderate to severe pain intensity which is not controlled with 300mg&#xD;
             of pregabalin per day for at least 1 week: NRS ≥ 4&#xD;
&#xD;
          -  Patients who need opioid combination treatment with existing pregabalin treatment&#xD;
&#xD;
          -  Naïve patients for strong opioid (Naïve patient defined as who did not treated for 90&#xD;
             days)&#xD;
&#xD;
          -  Patients who signed a written informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant. UNLESS they are:&#xD;
&#xD;
               -  women whose partners have been sterilized by vasectomy or other means&#xD;
&#xD;
               -  two birth control methods. The two methods can be a double barrier method or a&#xD;
                  barrier method plus a hormonal method. Adequate barrier methods of contraception&#xD;
                  include: diaphragm, condom (by the partner), intrauterine device (copper or&#xD;
                  hormonal), sponge or spermicidal. Hormonal contraceptives include any marketed&#xD;
                  contraceptive agent that includes an estrogen and/or (Progest - progesterone)&#xD;
                  progestational agent.&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive urine pregnancy test&#xD;
&#xD;
          -  Patients with known hypersensitivity to Oxycodone or Naloxone or to any of the&#xD;
             excipients&#xD;
&#xD;
          -  Patients with severe respiratory depression with hypoxia and/or hypercapnia&#xD;
&#xD;
          -  Patients with severe chronic obstructive pulmonary disease&#xD;
&#xD;
          -  Patients with cor pulmonale&#xD;
&#xD;
          -  Patients with severe bronchial asthma&#xD;
&#xD;
          -  Patients with non-opioid induced paralytic ileus&#xD;
&#xD;
          -  Patients with moderate to severe hepatic impairment&#xD;
&#xD;
          -  Targin product contains lactose. Patients with rare hereditary problems of galactose&#xD;
             intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not&#xD;
             take&#xD;
&#xD;
          -  Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT),&#xD;
             or alkaline phosphatase levels (&gt;2.5 times the upper limit of normal, it is allowed &gt;5&#xD;
             times the upper limit of normal in case of transition in liver) or an abnormal total&#xD;
             bilirubin and/or creatinine level(s) (greater than 1.5 times the upper limit of&#xD;
             normal), gamma glutamyl transpeptidase (GGT or GGTP) ≥ 3 times the upper limit of&#xD;
             normal&#xD;
&#xD;
          -  Patients with uncontrolled seizures&#xD;
&#xD;
          -  Requiring interventional treatment for pain such as neural blockade procedure or&#xD;
             regional infusion&#xD;
&#xD;
          -  Patients with increased intracranial pressure&#xD;
&#xD;
          -  In the investigator's opinion, subjects who are receiving hypnotics or other central&#xD;
             nervous system (CNS) depressants that may pose a risk of additional CNS depression&#xD;
             with opioid study medication&#xD;
&#xD;
          -  Patients with myxoedema, not adequately treated hypothyroidism or Addison's disease&#xD;
&#xD;
          -  Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or&#xD;
             buprenorphine)&#xD;
&#xD;
          -  Clinically significant impairment of cardiovascular, respiratory and renal function&#xD;
&#xD;
          -  Major surgery within 1 month prior to screening or planned surgery&#xD;
&#xD;
          -  Chemotherapy or radiotherapy within 2 weeks prior to the screening visit, or planned&#xD;
             chemotherapy or radiotherapy during the study period.&#xD;
&#xD;
          -  Mainly pain originated other than Chemotherapy-Induced Peripheral Neuropathy&#xD;
&#xD;
          -  Patients with diabetic neuropathy&#xD;
&#xD;
          -  With a disability that may prevent the patient from completing all study requirements&#xD;
             and in particular, interfere with 24hrs pain intensity score&#xD;
&#xD;
          -  Patients known to have, or suspected of having a history of drug abuse&#xD;
&#xD;
          -  Patients with history of opioid or drug dependence&#xD;
&#xD;
          -  Any situation where opioids are contraindicated&#xD;
&#xD;
          -  Having used other investigational drugs at the time of enrollment, or within 30 days&#xD;
             of enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kang, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul ST.Mary Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul ST.Mary Hospital</name>
      <address>
        <city>Seoul</city>
        <state>Banpogu</state>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <results_first_submitted>July 5, 2016</results_first_submitted>
  <results_first_submitted_qc>October 25, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 16, 2016</results_first_posted>
  <last_update_submitted>October 25, 2016</last_update_submitted>
  <last_update_submitted_qc>October 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 16, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Targin</keyword>
  <keyword>Chemotherapy Induced Peripheral Neuropathy (CIPN)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Safety set: 72 subjects ITT set: 66 subjects PP set: 41 subjects.</recruitment_details>
      <pre_assignment_details>73 Patients was enrolled. However, 1 patient was not administered investigational drug. So the patient excluded from safety set.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Oxycontin/Naloxone</title>
          <description>Targin(Oxycontin/Naloxone)&#xD;
Targin: Single arm for Targin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety set: 72 subjects</population>
      <group_list>
        <group group_id="B1">
          <title>Oxycodone/Naloxone</title>
          <description>Targin&#xD;
Targin: Single arm for Targin</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="72"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="62.97" spread="8.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>18~29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30~39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40~49</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50~59</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60~69</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;70</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>NRS (Numeric Rating Scale)</title>
        <description>Change of pain intensity score via NRS after vist 4 weeks treatment from baseline (week 0).&#xD;
NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week4/ET minus mean score at Baseline.</description>
        <time_frame>4 weeks</time_frame>
        <population>Analysis of ITT population set. Missing data was handled as LOCF(Last Observation Carried Forward Method).</population>
        <group_list>
          <group group_id="O1">
            <title>Oxycodone/Naloxone</title>
            <description>Targin&#xD;
Targin: Single arm for Targin</description>
          </group>
        </group_list>
        <measure>
          <title>NRS (Numeric Rating Scale)</title>
          <description>Change of pain intensity score via NRS after vist 4 weeks treatment from baseline (week 0).&#xD;
NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week4/ET minus mean score at Baseline.</description>
          <population>Analysis of ITT population set. Missing data was handled as LOCF(Last Observation Carried Forward Method).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.29" spread="1.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in FACT-GOG/NTX From Visit1(Week 0) to Visit 4(Week 4 Post-treatment).</title>
        <description>Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FAICT-GOG/NTX).&#xD;
The mean changes in FACT/GOG-NTX total score and each FACT/GOG-NTX subscale score from Visit 1 (Week 0) to Visit 4 (Week 4 post-treatment) were analyzed. Missing data was handled as LOCF(Last Observation Carried Forward Method).&#xD;
FACT/GOG-NTX total score range was from 0 to 152. The average change score from baseline to visit 4 indicates thay a lower score on the FACT/GOG-NTX means lower quality of life and a greater impact of neurotoxic symptom on the patient's life.</description>
        <time_frame>4 weeks</time_frame>
        <population>Analysis of ITT population set.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxycontin/Naloxone</title>
            <description>Targin(Oxycontin/Naloxone)&#xD;
Targin: Single arm for Targin</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in FACT-GOG/NTX From Visit1(Week 0) to Visit 4(Week 4 Post-treatment).</title>
          <description>Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FAICT-GOG/NTX).&#xD;
The mean changes in FACT/GOG-NTX total score and each FACT/GOG-NTX subscale score from Visit 1 (Week 0) to Visit 4 (Week 4 post-treatment) were analyzed. Missing data was handled as LOCF(Last Observation Carried Forward Method).&#xD;
FACT/GOG-NTX total score range was from 0 to 152. The average change score from baseline to visit 4 indicates thay a lower score on the FACT/GOG-NTX means lower quality of life and a greater impact of neurotoxic symptom on the patient's life.</description>
          <population>Analysis of ITT population set.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.78" spread="17.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Physician's Overall Satisfaction</title>
        <description>Physician's overall satisfaction was scored 7 scales from Very much worse to Very much improved. (Very much worse, much worse, minimally worse, No change, Minimally improved, much improved, very much improved).</description>
        <time_frame>4 weeks</time_frame>
        <population>Analysis of ITT population set.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxycontin/Naloxone</title>
            <description>Targin(Oxycontin/Naloxone)&#xD;
Targin: Single arm for Targin</description>
          </group>
        </group_list>
        <measure>
          <title>Physician's Overall Satisfaction</title>
          <description>Physician's overall satisfaction was scored 7 scales from Very much worse to Very much improved. (Very much worse, much worse, minimally worse, No change, Minimally improved, much improved, very much improved).</description>
          <population>Analysis of ITT population set.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>minimally worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient's Overall Satisfaction</title>
        <description>Patient's overall satisfaction was assessed 7 scales from very much worse to very much improved. (Very much worse, much worse, minimally worse, no change, minimally improved, much improved, very much improved)</description>
        <time_frame>4weeks</time_frame>
        <population>Analysis of ITT population set.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxycontin/Naloxone</title>
            <description>Targin(Oxycontin/Naloxone)&#xD;
Targin: Single arm for Targin</description>
          </group>
        </group_list>
        <measure>
          <title>Patient's Overall Satisfaction</title>
          <description>Patient's overall satisfaction was assessed 7 scales from very much worse to very much improved. (Very much worse, much worse, minimally worse, no change, minimally improved, much improved, very much improved)</description>
          <population>Analysis of ITT population set.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oxycodone/Naloxone</title>
          <description>Targin(Oxycodone/Naloxone)&#xD;
Targin: Single arm for Targin</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <description>Severity was severe and causality was not suspected with investigational drug(Oxycodone/Naloxone).&#xD;
Action taken was not changed to dose of investigational drug. However, Eventually, patient was withdrawal to study by herself.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Mental inpairment</sub_title>
                <description>Severity was mild and causality was not suspected. Action taken of study drug was not changed. The patient was completed to study by the end without drop out.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (10.0)</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="25" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (10.1)">Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (10.2)">Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (10.3)">Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
              </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>Jin-Hyong Kang</name_or_title>
      <organization>Seoul ST.Mary's Hospital</organization>
      <phone>82-2-2258-6043</phone>
      <email>jinkang@catholic.ac.kr</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/NCT01675531
org study id: OXN12-KR-402
nct id: NCT01675531
lead sponsor: 
has dmc: No
A multicenter, phase IV, interventional study to assess the efficacy and safety of Targin
      (Oxycodone/Naloxone) Korean patients with CIPN (Chemotherapy-Induced Peripheral Neuropathy)
      who need opioid combination treatment with existing pregabalin of last dose prior to study
      enrollment without changing.

      The investigators will assess study objectives as below.

      Primary objective

        -  To assess the pain reduction rate after 4 weeks treatment from baseline (week 0)

      Secondary objectives

        -  To assess the Functional Assessment of Cancer Therapy/Gynecologic Oncology
           Group-Neurotoxicity (FACIT-GOG/NTX)

        -  To assess physician's overall satisfaction

        -  To assess subject's overall satisfaction

        -  To assess safety

      The investigators have a hypothesis that Targin will show favorable efficacy & safety profile
      for CIPN patients.
This will be a multicenter, phase IV, interventional study to assess the efficacy and safety
      of Targin (Oxycodone/Naloxone) Korean patients with CIPN(Chemotherapy-Induced Peripheral
      Neuropathy) who need opioid combination treatment with existing pregabalin of last dose prior
      to study enrollment without changing.

      Upon providing written informed consent, subject will be screened in the study and assessment
      will be performed at that time such as safety data (adverse event (AE)/serious adverse events
      (SAEs)) including laboratory results, physical examination, vital sign, medical history
      taking, 24 hours pain intensity score, Functional Assessment of Cancer Therapy/Gynecologic
      Oncology Group-Neurotoxicity (FACT-GOG/NTX), physician's overall satisfaction and subject's
      overall satisfaction. If patient is eligible in inclusion/exclusion criteria at the time of
      visit 1, the patient will receive treatment with Targin. Re-screening, study drug dose
      interruption is not allowed. The duration of study drug dose interruption is defined as for 1
      week.

      Treatment with Targin will be started at 10/5mg twice daily for 4 weeks, and proper titration
      (up-titration) will be allowed at each visit according to the investigator's decision. Dose
      titration up to a maximum of Targin 40/20mg twice daily will be permitted during study
      period.

      The up-titration will be considered by investigator's judgement as followings; (1) if the
      rescue medication was used more than 2 times per day, on average or (2) based on the daily
      average Numeric Rating Scale (NRS), if the NRS was changed to worsen since the previous
      visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose,
      frequency of rescue medication).

      Safety laboratories will be obtained at baseline (visit 1) and study end (visit 4) in a local
      laboratory. The laboratory values within 4 weeks prior to baseline (visit 1) will be allowed
      to use at study visit 1.

      The rescue medication is the 5mg of (Immediate release codon trade mark)IRcodonTM .

      Patients will be withdrawn from the study if the following circumstance require study drug
      discontinuation:

      Failure of pain control (Failure of pain control will be decided by investigators judgement,
      e.g. there is poor pain control or lack of efficacy despite 2~3 times of up titration.)
      Adjustment of the other analgesics due to AEs except Targin or IRcodonTM Adjustment of the
      other major pain management modality (e.g. chemotherapy, radiotherapy, surgery, non-surgical
      interventional therapy, etc.) Withdrawal of informed consent Pregnancy Any other significant
      risk to the patient's safety in the clinical judgement of the investigator
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: NRS (Numeric Rating Scale)
time frame: 4 weeks
description: Change of pain intensity score via NRS after vist 4 weeks treatment from baseline (week 0).
NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week4/ET minus mean score at Baseline.
measure: Mean Change in FACT-GOG/NTX From Visit1(Week 0) to Visit 4(Week 4 Post-treatment).
time frame: 4 weeks
description: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FAICT-GOG/NTX).
The mean changes in FACT/GOG-NTX total score and each FACT/GOG-NTX subscale score from Visit 1 (Week 0) to Visit 4 (Week 4 post-treatment) were analyzed. Missing data was handled as LOCF(Last Observation Carried Forward Method).
FACT/GOG-NTX total score range was from 0 to 152. The average change score from baseline to visit 4 indicates thay a lower score on the FACT/GOG-NTX means lower quality of life and a greater impact of neurotoxic symptom on the patient's life.
measure: Physician's Overall Satisfaction
time frame: 4 weeks
description: Physician's overall satisfaction was scored 7 scales from Very much worse to Very much improved. (Very much worse, much worse, minimally worse, No change, Minimally improved, much improved, very much improved).
measure: Patient's Overall Satisfaction
time frame: 4weeks
description: Patient's overall satisfaction was assessed 7 scales from very much worse to very much improved. (Very much worse, much worse, minimally worse, no change, minimally improved, much improved, very much improved)
arm group label: Targin
arm group type: Experimental
description: Targin
intervention type: Drug
intervention name: Targin
description: Single arm for Targin
arm group label: Targin
other name: Oxycodone and Naloxone
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Kang, Ph.D
role: Principal Investigator
affiliation: Seoul ST.Mary Hospital
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Oxycodone
mesh term: Naloxone
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 