<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/NCT01726816</url>
  </required_header>
  <id_info>
    <org_study_id>009-KOA-1201i</org_study_id>
    <nct_id>NCT01726816</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Probucol in Patients With Diabetic Nephropathy</brief_title>
  <official_title>A Phase II, Multicenter, Randomized, Double Blind, Double-dummy, 16-week, Placebo Controlled Study to Evaluate the Efficacy and Safety of Probucol in Patients With Nephropathy Due to Type 2 Diabetes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Korea Otsuka Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is randomized, placebo-controlled, double blind, double dummy, multi-centre trial.&#xD;
&#xD;
        -  Screening period (4 week)&#xD;
&#xD;
        -  Double blind treatment period (16 weeks)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Usage: 16 week, BID, Prescribed Oral with the breakfast and dinner&#xD;
&#xD;
        2. Dosage:Placebo group: placebo 2 tablets, 16 weeks Probucol 250mg group: probucol 125mg 2&#xD;
           tablets, 16 weeks Probucol 500mg group: probucol 250 mg 2 tablets, 16 weeks&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A/C ratio</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the A/C ratio from baseline to the end of treatment(16 week) [Time Frame: baseline to 16 weeks]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the Serum creatinine from baseline to the end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the eGFR from baseline to the end of treatment(16 week)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cystatin C</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the cystatin C from baseline to the end of treatment(16 week)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>urine albumin</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the urine albumin from baseline to the end of treatment(16 week)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P/C ratio</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the P/C ratio from baseline to the end of treatment(16 week)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total Cholesterol</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the Total cholesterol from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>Triglyceride</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the Triglyceride from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>LDL-C</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the LDL-C from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>HDL-C</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the HDL-C from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>oxidized LDL</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the oxidized LDL from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>d-ROM</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the d-ROM from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>urinary fibronectin</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the urinary fibronectin from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>urinary transferrin</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the urinary transferrin from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>insulin</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the insulin from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <other_outcome>
    <measure>c-peptide</measure>
    <time_frame>16 week</time_frame>
    <description>The change in the c-peptide from baseline to the end of treatment(16 week)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Diabetic Nephropathy</condition>
  <arm_group>
    <arm_group_label>Probucol 250mg/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Probucol 500mg/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo group: placebo 2 tablets, 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probucol 250mg/day</intervention_name>
    <description>Probucol 250mg + Placebo</description>
    <arm_group_label>Probucol 250mg/day</arm_group_label>
    <other_name>Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probucol 500mg/day</intervention_name>
    <description>Probucol 500mg + Placebo</description>
    <arm_group_label>Probucol 500mg/day</arm_group_label>
    <other_name>Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Probucol matching placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>placebo 2 tablets, 16 weeks</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is male or female diagnosed with type 2 diabetes mellitus and must be aged&#xD;
             20 to 75 years at the time of screening visit&#xD;
&#xD;
          2. Urinary albumin excretion &gt; 300 mg/g Cr at screening visit&#xD;
&#xD;
          3. Subjects administered ACEI or ARB without changing dosage prior to 3 months at the&#xD;
             screening visit (if subjects administered ACEI or ARB)&#xD;
&#xD;
          4. Subjects administered statins without changing dosage prior to 3 months at the&#xD;
             screening visit(if subjects administered statins) or subjects have no plan to&#xD;
             administered to statin(if subjects is not administered statin)&#xD;
&#xD;
          5. 15 mL/min ≤ eGFR ≤ 90 mL min&#xD;
&#xD;
          6. Subjects must be willing and able to give signed and dated written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Type 1 DM or gestational diabetes&#xD;
&#xD;
          2. Subjects on Renal replacement therapy or Renal transplantation prior to Screening&#xD;
             visit&#xD;
&#xD;
          3. Ventricular arrhythmia (multiple and multifocal premature ventricular contractions)&#xD;
&#xD;
          4. Cardiac damage (abnormally levels of Troponin I)&#xD;
&#xD;
          5. Subject with medical history of cardiac syncope or primary syncope&#xD;
&#xD;
          6. Has condition that may prolong QTc interval (for man QTc interval&gt;450msec, for woman&#xD;
             QTc interval&gt;470msec) at screening&#xD;
&#xD;
          7. Pregnant or lactating woman before randomization&#xD;
&#xD;
          8. Inflammatory bowel disease (ulcerative colitis, Crohn's disease)&#xD;
&#xD;
          9. Cholestasis&#xD;
&#xD;
         10. Congestive heart failure&#xD;
&#xD;
         11. Subjects with a myocardial infarction, Unstable angina, or cerebral infarction within&#xD;
             the latest 6 months&#xD;
&#xD;
         12. Subjects has a diagnosis of NYHA grade III-IV status&#xD;
&#xD;
         13. AST or ALT is 3.0 times higher than the upper limit of the normal range&#xD;
&#xD;
         14. Active hepatitis Or Liver cirrhosis&#xD;
&#xD;
         15. Subjects with Hyperkalemia (K&gt;5.5 mEq/L)&#xD;
&#xD;
         16. Subjects with Renal Artery stenosis&#xD;
&#xD;
         17. Subjects with Malignancy within the 5 years at the time of screening visit(except for&#xD;
             treated Basal cells carcinoma or squamous cell carcinoma)&#xD;
&#xD;
         18. Urinary tract disease (urinary tract infection, Neurogenic bladder)&#xD;
&#xD;
         19. Kidney disease (nephritis, chronic glomerulonephritis or polycystic kidney disease)&#xD;
&#xD;
         20. Has an allergic history to probucol&#xD;
&#xD;
         21. HbA1c &gt; 9%&#xD;
&#xD;
         22. Systolic blood pressure ≥ 160 mmHg or Diastolic blood pressure ≥ 100 mmHg&#xD;
&#xD;
         23. Subjects taken probucol within 3 months prior to Screening&#xD;
&#xD;
         24. The subject has received an investigational product or biological agent within 3&#xD;
             months prior to screening&#xD;
&#xD;
         25. Subjects otherwise judged by the investigator or sub investigator to be inappropriate&#xD;
             for inclusion in the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MoonKyu Lee, professor</last_name>
    <role>Study Chair</role>
    <affiliation>Samsung Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Catholic university of Korea, Bucheon St. Mary's Hospital</name>
      <address>
        <city>Bucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University</name>
      <address>
        <city>DaeGu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yeungnam University Medical Center</name>
      <address>
        <city>DaeGu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gil Hospital</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inha University Hospital</name>
      <address>
        <city>InCheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonbuk national University Hospital</name>
      <address>
        <city>JeonJu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eulji Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kangbuk Samsung Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kangnam Sacred Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Guro Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyunghee Univ Hospital at Kangdong</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsumg Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>SungNam</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Hospital</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UIJEONGBU ST. MARY's HOSPITAL</name>
      <address>
        <city>Uijeongbu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetic nephropathy</keyword>
  <keyword>Albumin creatinine ratio</keyword>
  <keyword>Probucol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Probucol</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01726816
org study id: 009-KOA-1201i
nct id: NCT01726816
lead sponsor: 
has dmc: No
This trial is randomized, placebo-controlled, double blind, double dummy, multi-centre trial.

        -  Screening period (4 week)

        -  Double blind treatment period (16 weeks)
1. Usage: 16 week, BID, Prescribed Oral with the breakfast and dinner

        2. Dosage:Placebo group: placebo 2 tablets, 16 weeks Probucol 250mg group: probucol 125mg 2
           tablets, 16 weeks Probucol 500mg group: probucol 250 mg 2 tablets, 16 weeks
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: A/C ratio
time frame: 16 week
description: The change in the A/C ratio from baseline to the end of treatment(16 week) [Time Frame: baseline to 16 weeks]
measure: Serum creatinine
time frame: 16 week
description: The change in the Serum creatinine from baseline to the end of treatment.
measure: eGFR
time frame: 16 week
description: The change in the eGFR from baseline to the end of treatment(16 week)
measure: cystatin C
time frame: 16 week
description: The change in the cystatin C from baseline to the end of treatment(16 week)
measure: urine albumin
time frame: 16 week
description: The change in the urine albumin from baseline to the end of treatment(16 week)
measure: P/C ratio
time frame: 16 week
description: The change in the P/C ratio from baseline to the end of treatment(16 week)
measure: Total Cholesterol
time frame: 16 week
description: The change in the Total cholesterol from baseline to the end of treatment(16 week)
measure: Triglyceride
time frame: 16 week
description: The change in the Triglyceride from baseline to the end of treatment(16 week)
measure: LDL-C
time frame: 16 week
description: The change in the LDL-C from baseline to the end of treatment(16 week)
measure: HDL-C
time frame: 16 week
description: The change in the HDL-C from baseline to the end of treatment(16 week)
measure: oxidized LDL
time frame: 16 week
description: The change in the oxidized LDL from baseline to the end of treatment(16 week)
measure: d-ROM
time frame: 16 week
description: The change in the d-ROM from baseline to the end of treatment(16 week)
measure: urinary fibronectin
time frame: 16 week
description: The change in the urinary fibronectin from baseline to the end of treatment(16 week)
measure: urinary transferrin
time frame: 16 week
description: The change in the urinary transferrin from baseline to the end of treatment(16 week)
measure: insulin
time frame: 16 week
description: The change in the insulin from baseline to the end of treatment(16 week)
measure: c-peptide
time frame: 16 week
description: The change in the c-peptide from baseline to the end of treatment(16 week)
arm group label: Probucol 250mg/day
arm group type: Experimental
description: Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks
arm group label: Probucol 500mg/day
arm group type: Experimental
description: Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo group: placebo 2 tablets, 16 weeks
intervention type: Drug
intervention name: Probucol 250mg/day
description: Probucol 250mg + Placebo
arm group label: Probucol 250mg/day
other name: Probucol 250mg group: probucol 250mg 2 tablets, 16 weeks
intervention type: Drug
intervention name: Probucol 500mg/day
description: Probucol 500mg + Placebo
arm group label: Probucol 500mg/day
other name: Probucol 500mg group: probucol 250mg 2 tablets, 16 weeks
intervention type: Drug
intervention name: Placebo
description: Probucol matching placebo
arm group label: Placebo
other name: placebo 2 tablets, 16 weeks
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: MoonKyu Lee, professor
role: Study Chair
affiliation: Samsung Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Probucol