<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/NCT02230670</url>
  </required_header>
  <id_info>
    <org_study_id>IDN-6556-10</org_study_id>
    <nct_id>NCT02230670</nct_id>
  </id_info>
  <brief_title>A Study of IDN-6556 in Subjects With Liver Cirrhosis</brief_title>
  <acronym>LC</acronym>
  <official_title>A Multicenter, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Subjects With Liver Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Conatus Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Conatus Pharmaceuticals Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter study to see if treatment with IDN-6556 can help improve the liver&#xD;
      function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores&#xD;
      between 11-18.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous studies have shown that caspase cleaved cytokeratin 18 (cCK18) is elevated in the&#xD;
      serum of liver disease patients and has been associated with disease severity, thus&#xD;
      associating both excessive apoptosis and caspase activity with disease. Studies have also&#xD;
      shown that caspase cleaved cytokeratin 18 is generally elevated to an even greater degree in&#xD;
      cirrhosis than in other liver diseases. In addition, increasing stages of cirrhosis from&#xD;
      Child-Pugh A, Child-Pugh B to Child-Pugh C are associated with progressively higher levels of&#xD;
      caspase cleaved cytokeratin 18. Therefore, it appears that apoptosis and caspase activity&#xD;
      tend to correlate with the stage of cirrhosis. A caspase inhibitor like IDN-6556 could have&#xD;
      clinical utility by reducing the rate of apoptosis in cirrhotic patients and potentially&#xD;
      reduce the progression of disease as determined by clinical markers of progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline at Month 3 in cCK18/M30</measure>
    <time_frame>3 months</time_frame>
    <description>Baseline, Month 3, and change between for cCK18/M30</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline at Month 3 in cCK18/M30</measure>
    <time_frame>3 months</time_frame>
    <description>Data was log-transformed for analysis purposes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 3 in MELD Score</measure>
    <time_frame>3 Months</time_frame>
    <description>The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:&#xD;
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43&#xD;
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Hepatic Cirrhosis</condition>
  <arm_group>
    <arm_group_label>IDN-6556</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 mg BID of IDN-6556</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IDN-6556</intervention_name>
    <description>25 mg BID</description>
    <arm_group_label>IDN-6556</arm_group_label>
    <other_name>emricasan</other_name>
    <other_name>PF-03491390</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects of minimum adult legal age (according to local laws for&#xD;
             signing the informed consent document), able to provide written informed consent, and&#xD;
             able to understand and willing to comply with the requirements of the study&#xD;
&#xD;
          -  Clinical, radiological, or biochemical evidence of liver cirrhosis&#xD;
&#xD;
          -  Model for End-Stage Liver Disease (MELD) Score of 11 to 18 during the Screening period&#xD;
&#xD;
          -  Willingness to utilize two reliable forms of contraception (for both males and females&#xD;
             of childbearing potential) from Screening to one month after the last dose of study&#xD;
             drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Auto-immune hepatitis&#xD;
&#xD;
          -  Subjects with evidence of uncontrolled infection, defined as persistent bacterial&#xD;
             culture positivity despite adequate antibiotic therapy&#xD;
&#xD;
          -  HCV infected subjects who are receiving or plan to receive anti-viral therapy during&#xD;
             the study&#xD;
&#xD;
          -  Untreated esophageal varices with high risk stigmata for hemorrhage&#xD;
&#xD;
          -  Variceal hemorrhage within 3 months of Screening&#xD;
&#xD;
          -  Ascites not adequately controlled on stable background medication&#xD;
&#xD;
          -  Other non-liver organ failure&#xD;
&#xD;
          -  Child-Pugh score of 10-15 (Child-Pugh C classification)&#xD;
&#xD;
          -  Use of vasoactive drugs (at or within 3 months of Screening) that may impair hepatic&#xD;
             blood flow&#xD;
&#xD;
          -  Change in dose or regimen within 3 months of Screening of:&#xD;
&#xD;
               1. Fibrates or statins&#xD;
&#xD;
               2. Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE)&#xD;
                  inhibitor&#xD;
&#xD;
          -  Use of chronic anticoagulation therapy including but not limited to Vitamin K/Factor&#xD;
             Xa antagonists/inhibitors&#xD;
&#xD;
          -  Use of the following drugs within 2 months of Screening:&#xD;
&#xD;
               1. Systemic corticosteroids&#xD;
&#xD;
               2. Known or suspected use of illicit drugs or drugs of abuse (allowed if medically&#xD;
                  prescribed or indicated)&#xD;
&#xD;
          -  Concomitant pancreatitis&#xD;
&#xD;
          -  Active inflammatory bowel disease&#xD;
&#xD;
          -  Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis&#xD;
             (RA)&#xD;
&#xD;
          -  Subjects with active or history of malignancies other than hepatocellular carcinoma&#xD;
             (HCC) within Milan criteria or curatively treated skin cancer (basal cell or squamous&#xD;
             cell carcinomas), unless adequately treated or in complete remission for five or more&#xD;
             years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dave Hagerty, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Conatus Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scripps Clinic</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loma Linda University Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedar-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univeristy of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Atlanta Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Cente</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers New Jersey Medical School</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mt. Sinai School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Physicians Company, LLC</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Einstein Healthcare Network</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor All Saints Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor St. Luke's Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Mary Immaculate Hospital</name>
      <address>
        <city>Newport News</city>
        <state>Virginia</state>
        <zip>23602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours St. Mary's Hospital of Richmond, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <results_first_submitted>January 27, 2017</results_first_submitted>
  <results_first_submitted_qc>June 6, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 5, 2017</results_first_posted>
  <last_update_submitted>June 6, 2017</last_update_submitted>
  <last_update_submitted_qc>June 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver Cirrhosis</keyword>
  <keyword>Hepatic Cirrhosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 140 subjects from 26 US sites were screened, of whom 87 subjects were randomized. One subject randomized to placebo withdrew from the study before taking study drug. Disposition data is provided for the initial 3-month randomized, placebo-controlled phase on which the primary efficacy and safety analyses were based</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>IDN-6556</title>
          <description>25 mg BID of IDN-6556&#xD;
IDN-6556: 25 mg BID</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo BID&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="42">One subject randomized to placebo withdrew from the study before receiving any study treatment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression to Child-Pugh C</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>IDN-6556</title>
          <description>25 mg BID of IDN-6556&#xD;
IDN-6556: 25 mg BID</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo BID&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <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="44"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="86"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </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="20"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="54"/>
                  </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="6"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline at Month 3 in cCK18/M30</title>
        <description>Baseline, Month 3, and change between for cCK18/M30</description>
        <time_frame>3 months</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>25 mg BID of IDN-6556&#xD;
IDN-6556: 25 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo BID&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Month 3 in cCK18/M30</title>
          <description>Baseline, Month 3, and change between for cCK18/M30</description>
          <population>FAS</population>
          <units>U/L</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="293.5" lower_limit="66" upper_limit="1857"/>
                    <measurement group_id="O2" value="257.5" lower_limit="104" upper_limit="6994"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="288.5" lower_limit="39" upper_limit="1583"/>
                    <measurement group_id="O2" value="285.0" lower_limit="115" upper_limit="19710"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline at Month 3 in cCK18/M30</title>
        <description>Data was log-transformed for analysis purposes</description>
        <time_frame>3 months</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>25 mg BID of IDN-6556&#xD;
IDN-6556: 25 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo BID&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Month 3 in cCK18/M30</title>
          <description>Data was log-transformed for analysis purposes</description>
          <population>Full analysis set</population>
          <units>U/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Log-transformed Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.049" spread="0.057"/>
                    <measurement group_id="O2" value="0.090" spread="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent (%) Relative Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.6" spread="5.9"/>
                    <measurement group_id="O2" value="9.3" spread="5.9"/>
                  </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>Analysis was conducted using an ANCOVA model adjusting for baseline value.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.091</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.140</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0817</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.302</ci_lower_limit>
            <ci_upper_limit>0.023</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The analysis was conducted using an ANCOVA model adjusting for baseline value, baseline MELD score, and etiology. The significance was assessed using Type II Sums of Squares from this ANCOVA model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.041</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.20</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.210</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.41</ci_lower_limit>
            <ci_upper_limit>0.01</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 3 in MELD Score</title>
        <description>The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:&#xD;
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43&#xD;
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.</description>
        <time_frame>3 Months</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>25 mg BID of IDN-6556&#xD;
IDN-6556: 25 mg BID</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo BID&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 3 in MELD Score</title>
          <description>The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:&#xD;
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43&#xD;
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.</description>
          <population>FAS</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.234"/>
                    <measurement group_id="O2" value="0.15" spread="0.239"/>
                  </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>Analysis was conducted using an ANCOVA model adjusting for baseline value.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.466</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.24</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.333</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.91</ci_lower_limit>
            <ci_upper_limit>0.42</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>BL MELD &gt;= 15 subgroup results (N=19), as analyzed from the adjusted analysis ANCOVA model adjusting for baseline value, baseline MELD score, and etiology.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>ANCOVA</method>
            <method_desc>calculated from the estimated least square means for the treatment by BL MELD category interaction term.</method_desc>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-2.19</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.42</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.61</ci_lower_limit>
            <ci_upper_limit>-0.77</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>NASH Etiology subgroup results (N=20), as analyzed from the adjusted analysis ANCOVA model adjusting for baseline value, baseline MELD score, and etiology.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.029</p_value>
            <method>ANCOVA</method>
            <method_desc>calculated from the estimated least square means for the treatment by etiology interaction term.</method_desc>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.46</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.09</ci_lower_limit>
            <ci_upper_limit>-0.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected in a blinded fashion from baseline to Month 3. Double-blind adverse events are presented here</time_frame>
      <group_list>
        <group group_id="E1">
          <title>IDN-6556 (Baseline-Month 3)</title>
          <description>25 mg BID of IDN-6556 (Baseline-Month 3).</description>
        </group>
        <group group_id="E2">
          <title>Placebo (Baseline-Month 3)</title>
          <description>Placebo BID (Baseline-Month 3)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hepatorenal syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Peritontis bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidential overdose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Stoma site heamorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Convulsions</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>intraventricular haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pulmonary alveolar haemorrage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (Unspecified)">ascites</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (Unspecified)">arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="44"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (Unspecified)">headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="44"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>hepatic encephalopathy</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="44"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jean L. Chan, MD</name_or_title>
      <organization>Conatus Pharmaceuticals</organization>
      <phone>(858) 376-2632</phone>
      <email>jchan@conatuspharma.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/NCT02230670
org study id: IDN-6556-10
nct id: NCT02230670
lead sponsor: 
has dmc: Yes
This is a multicenter study to see if treatment with IDN-6556 can help improve the liver
      function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores
      between 11-18.
Numerous studies have shown that caspase cleaved cytokeratin 18 (cCK18) is elevated in the
      serum of liver disease patients and has been associated with disease severity, thus
      associating both excessive apoptosis and caspase activity with disease. Studies have also
      shown that caspase cleaved cytokeratin 18 is generally elevated to an even greater degree in
      cirrhosis than in other liver diseases. In addition, increasing stages of cirrhosis from
      Child-Pugh A, Child-Pugh B to Child-Pugh C are associated with progressively higher levels of
      caspase cleaved cytokeratin 18. Therefore, it appears that apoptosis and caspase activity
      tend to correlate with the stage of cirrhosis. A caspase inhibitor like IDN-6556 could have
      clinical utility by reducing the rate of apoptosis in cirrhotic patients and potentially
      reduce the progression of disease as determined by clinical markers of progression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline at Month 3 in cCK18/M30
time frame: 3 months
description: Baseline, Month 3, and change between for cCK18/M30
measure: Change From Baseline at Month 3 in cCK18/M30
time frame: 3 months
description: Data was log-transformed for analysis purposes
measure: Change From Baseline to Month 3 in MELD Score
time frame: 3 Months
description: The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.
arm group label: IDN-6556
arm group type: Experimental
description: 25 mg BID of IDN-6556
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo BID
intervention type: Drug
intervention name: IDN-6556
description: 25 mg BID
arm group label: IDN-6556
other name: emricasan
other name: PF-03491390
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dave Hagerty, MD
role: Study Chair
affiliation: Conatus Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Fibrosis
participant flow: 
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reported events: 
certain agreements: 
point of contact: 