<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/NCT02230683</url>
  </required_header>
  <id_info>
    <org_study_id>IDN-6556-11</org_study_id>
    <nct_id>NCT02230683</nct_id>
  </id_info>
  <brief_title>A Study of IDN-6556 in Cirrhotic Subjects With Portal Hypertension</brief_title>
  <acronym>PH</acronym>
  <official_title>An Open-Label Pilot Trial to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Cirrhotic Subjects With Portal Hypertension</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 an open-label pilot study to evaluate the safety, tolerability, and efficacy of&#xD;
      IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Studies in patients with liver disease have demonstrated that cCK18 is elevated in the serum&#xD;
      of patients and has been associated with disease severity. Studies have also shown that cCK18&#xD;
      is generally elevated to a higher degree in cirrhosis than in other liver diseases. In&#xD;
      addition, increasing stages of cirrhosis from Child-Pugh A, Child-Pugh B to Child-Pugh C are&#xD;
      associated with progressively higher levels of caspase cleaved cytokeratin 18. This suggests&#xD;
      that apoptosis and caspase activity are associated with the severity of disease. IDN-6556 and&#xD;
      its ability to inhibit inflammation and apoptosis may have a beneficial impact on both the&#xD;
      dynamic and structural components associated with the pathogenesis of portal hypertension in&#xD;
      cirrhosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hepatic Venous Pressure Gradient (HVPG)</measure>
    <time_frame>Baseline to Day 28/EOT (end of treatment)</time_frame>
    <description>Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cCK18/M30</measure>
    <time_frame>Change from Baseline to Day 28/EOT</time_frame>
    <description>Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cCK18/M30</measure>
    <time_frame>Baseline to Day 28/EOT (end of treatment)</time_frame>
    <description>Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Alanine Aminotransferase (ALT)</measure>
    <time_frame>Baseline to 28 days/EOT</time_frame>
    <description>Median change of ALT from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Aspartate Aminotransferase (AST)</measure>
    <time_frame>Baseline to 28 days/EOT</time_frame>
    <description>Median change of AST from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Caspase 3/7 RLU</measure>
    <time_frame>Baseline to 28 days/EOT</time_frame>
    <description>Median change of concentration of Caspase 3/7 Relative Light Units from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Hepatic Cirrhosis</condition>
  <condition>Portal Hypertension</condition>
  <arm_group>
    <arm_group_label>IDN-6556 - Overall population</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IDN-6556 - Subgroup with Baseline HVPG &lt; 12 mmHg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subgroup for patients with Baseline HVPG &lt; 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily</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 - Overall population</arm_group_label>
    <arm_group_label>IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg</arm_group_label>
    <arm_group_label>IDN-6556 - Subgroup with Baseline HVPG &lt; 12 mmHg</arm_group_label>
    <other_name>emricasan</other_name>
    <other_name>PF-013491390</other_name>
  </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;
          -  Evidence of portal hypertension as evidenced by any of the following:&#xD;
&#xD;
               1. Splenomegaly, on imaging and/or clinical evaluation, with platelet count of&#xD;
                  &lt;120,000 at study entry, or&#xD;
&#xD;
               2. Presence of small sized varices on screening endoscopy and/or collateral&#xD;
                  circulation on imaging, or&#xD;
&#xD;
               3. Presence of medium/large varices that have never bled and have been obliterated&#xD;
                  with endoscopic ligation&#xD;
&#xD;
          -  Portal hypertension defined as a hepatic venous pressure gradient (HVPG) &gt;5 mmHg at&#xD;
             Screening&#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;
          -  Decompensated cirrhosis as defined by the presence of overt ascites (requiring&#xD;
             diuretics), overt encephalopathy (requiring specific therapy), or history of variceal&#xD;
             hemorrhage.&#xD;
&#xD;
          -  Known infection with HIV&#xD;
&#xD;
          -  Hepatic failure defined as total bilirubin ≥12 mg/dL&#xD;
&#xD;
          -  Other non-liver organ failure, including:&#xD;
&#xD;
               1. Renal failure defined as creatinine ≥ 2.0 mg/dL&#xD;
&#xD;
               2. Cerebral failure defined as hepatic encephalopathy grade III or IV&#xD;
&#xD;
               3. Coagulation failure defined as INR ≥ 2.5 or platelets ≤ 20x109/L&#xD;
&#xD;
               4. Hemodynamic requirement for inotropic support&#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; examples include but are not limited to:&#xD;
&#xD;
               1. β-blockers, including carvedilol&#xD;
&#xD;
               2. Nitrates&#xD;
&#xD;
               3. Vasopressin (or analogues)&#xD;
&#xD;
               4. Phosphodiesterase inhibitors (prescribed daily for pulmonary hypertension; p.r.n.&#xD;
                  use for erectile dysfunction is permitted)&#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 the following drugs within 2 months of Screening:&#xD;
&#xD;
               1. Systemic corticosteroids&#xD;
&#xD;
               2. Pentoxifylline&#xD;
&#xD;
               3. Known or suspected use of illicit drugs or drugs of abuse (allowed if medically&#xD;
                  prescribed or indicated)&#xD;
&#xD;
          -  Concomitant pancreatitis&#xD;
&#xD;
          -  Evidence of portal vein thrombosis on Doppler ultrasound of the portal vasculature&#xD;
&#xD;
          -  Active inflammatory bowel disease&#xD;
&#xD;
          -  Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis&#xD;
             (RA)&#xD;
&#xD;
          -  Autoimmune hepatitis&#xD;
&#xD;
          -  Hepatitis C Virus (HCV) infected subjects receiving or planning on receiving&#xD;
             anti-viral therapy during the course of the study&#xD;
&#xD;
          -  Hepatitis B Virus (HBV) infected subjects who have been on stable anti-HBV therapy for&#xD;
             less than 3 months&#xD;
&#xD;
          -  Hepatocellular carcinoma (HCC) at entry into the study&#xD;
&#xD;
          -  Active non-liver malignancies other than curatively treated skin cancer (basal cell or&#xD;
             squamous cell carcinomas)&#xD;
&#xD;
          -  History or presence of clinically concerning cardiac arrhythmias, or prolongation of&#xD;
             screening (pre-treatment) QT or QTc interval of &gt;480 milliseconds (msec)&#xD;
&#xD;
          -  Significant systemic or major illness other than liver disease, including coronary&#xD;
             artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious&#xD;
             psychiatric disease, that, in the opinion of the Investigator would preclude the&#xD;
             subject from participating in and completing the study&#xD;
&#xD;
          -  Any subject that has received any investigational drug or device within 30 days of&#xD;
             dosing or who is scheduled to receive another investigational drug or device in the&#xD;
             course of the study&#xD;
&#xD;
          -  If female, known pregnancy, or has a positive urine or serum pregnancy test, or&#xD;
             lactating/breastfeeding.&#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>David Hagerty, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Conatus Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Sibley Memorial Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</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>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</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>New York University Lagone Medical Center</name>
      <address>
        <city>NYC</city>
        <state>New York</state>
        <zip>10016</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>Albert Einstein Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Health 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>University of Texas 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</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGuire DVAMC</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</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>June 28, 2016</results_first_submitted>
  <results_first_submitted_qc>October 28, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 21, 2016</results_first_posted>
  <last_update_submitted>October 28, 2016</last_update_submitted>
  <last_update_submitted_qc>October 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 21, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver Cirrhosis</keyword>
  <keyword>Hepatic Cirrhosis</keyword>
  <keyword>Portal Hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Hypertension, Portal</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>IDN-6556</title>
          <description>IDN-6556 25 mg Dosed twice daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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_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>IDN-6556 25 mg Dosed twice daily</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
          </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="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hepatic Venous Pressure Gradient (HVPG)</title>
        <description>Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Baseline to Day 28/EOT (end of treatment)</time_frame>
        <population>23 subjects were enrolled, of whom 22 were evaluable for the HVPG endpoint. 1 subject discontinued at day 1.</population>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556 - Overall Population</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily with HVPG measurement at Baseline and Day 28</description>
          </group>
          <group group_id="O2">
            <title>IDN-6556 - Subgroup With HVPG &lt; 12 mmHg</title>
            <description>Subgroup for patients with HVPG &lt; 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
          <group group_id="O3">
            <title>IDN-6556 - Subgroup HVPG ≥ 12 mmHg</title>
            <description>Subgroup for patients with HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Hepatic Venous Pressure Gradient (HVPG)</title>
          <description>Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <population>23 subjects were enrolled, of whom 22 were evaluable for the HVPG endpoint. 1 subject discontinued at day 1.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.2" spread="7.68"/>
                    <measurement group_id="O2" value="8.05" spread="1.88"/>
                    <measurement group_id="O3" value="20.62" spread="5.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28/EOT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.1" spread="6.40"/>
                    <measurement group_id="O2" value="10.0" spread="3.86"/>
                    <measurement group_id="O3" value="17.6" spread="6.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.14" spread="4.57"/>
                    <measurement group_id="O2" value="1.90" spread="3.15"/>
                    <measurement group_id="O3" value="-3.67" spread="4.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the mean change of the Hepatic Venous Pressure Gradient from Baseline to Day 28/EOT for the overall evaluable population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.257</p_value>
            <method>Paired t-test</method>
            <param_type>within group change</param_type>
            <param_value>-1.14</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>4.57</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.16</ci_lower_limit>
            <ci_upper_limit>0.89</ci_upper_limit>
            <estimate_desc>within group change</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the mean change of the Hepatic Venous Pressure Gradient from Baseline to Day 28/EOT in the HVPG &lt; 12 mmHg subgroup</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1174</p_value>
            <method>ANCOVA</method>
            <param_type>within group change</param_type>
            <param_value>1.90</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>3.15</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.52</ci_lower_limit>
            <ci_upper_limit>4.32</ci_upper_limit>
            <estimate_desc>within group change</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the mean change of the Hepatic Venous Pressure Gradient from Baseline to Day 28/EOT in the HVPG ≥ 12 mmHg subgroup</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0025</p_value>
            <method>ANCOVA</method>
            <param_type>within group change</param_type>
            <param_value>-3.67</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>4.05</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.88</ci_lower_limit>
            <ci_upper_limit>-1.46</ci_upper_limit>
            <estimate_desc>within group change</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>cCK18/M30</title>
        <description>Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Change from Baseline to Day 28/EOT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556 - Overall Population</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>IDN-6556 - Subgroup With HVPG &lt; 12 mmHg</title>
            <description>Subgroup for patients with Baseline HVPG &lt; 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
          <group group_id="O3">
            <title>IDN-6556 - Subgroup HVPG ≥ 12 mmHg</title>
            <description>Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>cCK18/M30</title>
          <description>Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-47.1" spread="122.23"/>
                    <measurement group_id="O2" value="-74.3" spread="99.02"/>
                    <measurement group_id="O3" value="-26.2" spread="137.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the mean change in log-transformed caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT for the overall evaluable population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.026</p_value>
            <method>ANCOVA</method>
            <param_type>within group change</param_type>
            <param_value>-0.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.42</ci_lower_limit>
            <ci_upper_limit>-0.03</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the mean change in log-transformed caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT in the HVPG &lt; 12 mmHg subgroup population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>ANCOVA</method>
            <param_type>within group change</param_type>
            <param_value>-0.46</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.72</ci_lower_limit>
            <ci_upper_limit>-0.21</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change in log-transformed caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT in the HVPG ≥ 12 mmHg subgroup population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.72</p_value>
            <method>ANCOVA</method>
            <param_type>within group change</param_type>
            <param_value>-0.04</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.26</ci_lower_limit>
            <ci_upper_limit>0.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in cCK18/M30</title>
        <description>Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Baseline to Day 28/EOT (end of treatment)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556 - Overall Population</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>IDN-6556 - Subgroup With HVPG &lt; 12 mmHg</title>
            <description>Subgroup for patients with HVPG &lt; 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
          <group group_id="O3">
            <title>IDN-6556 - Subgroup HVPG ≥ 12 mmHg</title>
            <description>Subgroup for patients with HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in cCK18/M30</title>
          <description>Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <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="23"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="191.0" lower_limit="78" upper_limit="994"/>
                    <measurement group_id="O2" value="189.0" lower_limit="126" upper_limit="442"/>
                    <measurement group_id="O3" value="221.0" lower_limit="78" upper_limit="994"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28/EOT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="143.0" lower_limit="48" upper_limit="548"/>
                    <measurement group_id="O2" value="124.5" lower_limit="48" upper_limit="291"/>
                    <measurement group_id="O3" value="186.0" lower_limit="94" upper_limit="548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline at Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.0" lower_limit="-446" upper_limit="119"/>
                    <measurement group_id="O2" value="-52.5" lower_limit="-323" upper_limit="45"/>
                    <measurement group_id="O3" value="12.0" lower_limit="-446" upper_limit="119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change of caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT for the overall evaluable population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.105</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>-21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-60</ci_lower_limit>
            <ci_upper_limit>13</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change of caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT in the HVPG &lt; 12 mmHg subgroup population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.016</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>-52.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-109</ci_lower_limit>
            <ci_upper_limit>-6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change of caspase-cleaved cytokeratin serum levels from Baseline to Day 28/EOT in the HVPG ≥ 12 mmHg subgroup population treated with IDN-6556 25 mg twice daily</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.839</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>12</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-60</ci_lower_limit>
            <ci_upper_limit>13</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alanine Aminotransferase (ALT)</title>
        <description>Median change of ALT from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Baseline to 28 days/EOT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alanine Aminotransferase (ALT)</title>
          <description>Median change of ALT from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.0" lower_limit="10" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28/EOT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.0" lower_limit="9" upper_limit="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" lower_limit="-61" upper_limit="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change in Alanine Aminotransferase (ALT) from Baseline to Day 28/EOT</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0084</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>-4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Aspartate Aminotransferase (AST)</title>
        <description>Median change of AST from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Baseline to 28 days/EOT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Aspartate Aminotransferase (AST)</title>
          <description>Median change of AST from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" lower_limit="16" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28/EOT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.0" lower_limit="13" upper_limit="139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" lower_limit="-29" upper_limit="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change in Aspartate Aminotransferase (AST) from Baseline to Day 28/EOT</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0131</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>-4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7</ci_lower_limit>
            <ci_upper_limit>-1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Concentration of Caspase 3/7 RLU</title>
        <description>Median change of concentration of Caspase 3/7 Relative Light Units from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
        <time_frame>Baseline to 28 days/EOT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IDN-6556</title>
            <description>Overall evaluable population treated with IDN-6556 25 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Caspase 3/7 RLU</title>
          <description>Median change of concentration of Caspase 3/7 Relative Light Units from Baseline to Day 28/EOT (end of treatment) for IDN-6556</description>
          <units>RLU</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1997" lower_limit="750" upper_limit="37428"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28/EOT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1518" lower_limit="276" upper_limit="3665"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-772" lower_limit="-34734" upper_limit="1107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Statistical Analysis for the median change in concentration of Caspase 3/7 Relative Light Units from baseline to Day 28/EOT</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges-Lehmann</param_type>
            <param_value>-772</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1188</ci_lower_limit>
            <ci_upper_limit>-19</ci_upper_limit>
            <estimate_desc>The estimated value is the ratio for the difference from baseline.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected for a period of 8 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>IDN-6556</title>
          <description>IDN-6556 25 mg Dosed twice daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</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="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Systematic inflammatory response syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (17.0)</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="15" subjects_at_risk="23"/>
              </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="2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye discharge</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Local swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Soft tissue inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Scratch</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Connective tissue disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Systemic lupus erythematosus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkeratosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </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 Inc.</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/NCT02230683
org study id: IDN-6556-11
nct id: NCT02230683
lead sponsor: 
has dmc: Yes
This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of
      IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.
Studies in patients with liver disease have demonstrated that cCK18 is elevated in the serum
      of patients and has been associated with disease severity. Studies have also shown that cCK18
      is generally elevated to a higher 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. This suggests
      that apoptosis and caspase activity are associated with the severity of disease. IDN-6556 and
      its ability to inhibit inflammation and apoptosis may have a beneficial impact on both the
      dynamic and structural components associated with the pathogenesis of portal hypertension in
      cirrhosis.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hepatic Venous Pressure Gradient (HVPG)
time frame: Baseline to Day 28/EOT (end of treatment)
description: Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556
measure: cCK18/M30
time frame: Change from Baseline to Day 28/EOT
description: Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556
measure: Change in cCK18/M30
time frame: Baseline to Day 28/EOT (end of treatment)
description: Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556
measure: Change in Alanine Aminotransferase (ALT)
time frame: Baseline to 28 days/EOT
description: Median change of ALT from Baseline to Day 28/EOT (end of treatment) for IDN-6556
measure: Change in Aspartate Aminotransferase (AST)
time frame: Baseline to 28 days/EOT
description: Median change of AST from Baseline to Day 28/EOT (end of treatment) for IDN-6556
measure: Concentration of Caspase 3/7 RLU
time frame: Baseline to 28 days/EOT
description: Median change of concentration of Caspase 3/7 Relative Light Units from Baseline to Day 28/EOT (end of treatment) for IDN-6556
arm group label: IDN-6556 - Overall population
arm group type: Experimental
description: Overall evaluable population treated with IDN-6556 25 mg twice daily
arm group label: IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg
arm group type: Experimental
description: Subgroup for patients with Baseline HVPG < 12 mmHg that have been treated with IDN-6556 25 mg twice daily
arm group label: IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg
arm group type: Experimental
description: Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily
intervention type: Drug
intervention name: IDN-6556
description: 25 mg BID
arm group label: IDN-6556 - Overall population
arm group label: IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg
arm group label: IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg
other name: emricasan
other name: PF-013491390
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Hagerty, MD
role: Study Chair
affiliation: Conatus Pharmaceuticals
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Hypertension, Portal
mesh term: Hypertension
mesh term: Fibrosis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 