<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/NCT01703169</url>
  </required_header>
  <id_info>
    <org_study_id>HCI54443</org_study_id>
    <secondary_id>ELT115895</secondary_id>
    <nct_id>NCT01703169</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia</brief_title>
  <official_title>Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesis is that eltrombopag given to patients with moderate to very&#xD;
      severe aplastic anemia will result in an increase in platelet counts. The investigators&#xD;
      hypothesize that in patients with moderate to very severe aplastic anemia, treatment with&#xD;
      eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer&#xD;
      bleeding events. The investigators hypothesize that in patients with moderate to very severe&#xD;
      aplastic anemia, eltrombopag will have an acceptable toxicity rate &lt;3%, at doses that result&#xD;
      in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag&#xD;
      levels in peripheral blood will correlate with improved platelet counts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants With Platelet Response</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet Count Twice Baseline.</measure>
    <time_frame>Between weeks 1-12.</time_frame>
    <description>Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematology Labs</measure>
    <time_frame>12 weeks</time_frame>
    <description>Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With AE to Measure Toxicity, Using NCI CTCAE</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.</measure>
    <time_frame>Weeks 2, 6 and 12</time_frame>
    <description>Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Severe Aplastic Anemia</condition>
  <condition>Very Severe Aplastic Anemia</condition>
  <condition>Moderate Aplastic Anemia</condition>
  <arm_group>
    <arm_group_label>Eltrombopag</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm study. Dose Escalation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eltrombopag</intervention_name>
    <description>Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
    <arm_group_label>Eltrombopag</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to provide written informed consent and any other authorizations required by&#xD;
             local law (e.g., Protected Health Information [PHI])&#xD;
&#xD;
          -  Have severe or very severe aplastic anemia, or moderate aplastic anemia with platelet&#xD;
             counts that have dropped below 20,000/μl&#xD;
&#xD;
          -  Have moderate, severe, or very severe aplastic anemia with moderate bleeding during or&#xD;
             after a surgical procedure, (including bone marrow biopsy, lumbar puncture,&#xD;
             thoracentesis, paracentesis, port placement, dermal biopsy) or minimal mucocutaneous&#xD;
             bleeding otherwise noted&#xD;
&#xD;
          -  Subjects with current or previous exposure to approved medications for the treatment&#xD;
             of aplastic anemia will not be excluded; these include but may not be limited to,&#xD;
             anti-thymocyte globulin (ATG), cyclosporine, corticosteroids, and G-CSF.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have diagnosis of Fanconi anemia&#xD;
&#xD;
          -  Have infection not adequately responding to appropriate therapy&#xD;
&#xD;
          -  Have Paroxysmal Nocturnal Hemoglobinuria (PNH) clone size in neutrophils of greater&#xD;
             than or equal to 50%&#xD;
&#xD;
          -  Have known HIV positivity&#xD;
&#xD;
          -  Have creatinine and/or blood urea nitrogen (BUN) ≥2 times the upper limit of normal&#xD;
&#xD;
          -  Have serum bilirubin ≥ 1.5 times the upper limit of normal, or ≥4.0 times the upper&#xD;
             limit of normal if the patient has been treated with ATG within three weeks of&#xD;
             screening.&#xD;
&#xD;
          -  Have AST and/or ALT ≥ 3 times the upper limit of normal&#xD;
&#xD;
          -  Have hypersensitivity to eltrombopag or its components&#xD;
&#xD;
          -  Have chemotherapy given less than or equal to 14 days prior to initiating the study&#xD;
             medication. This does not include immunosuppressive agents and growth factor as&#xD;
             described above&#xD;
&#xD;
          -  Are female and are nursing or pregnant or are unwilling to take oral contraceptives or&#xD;
             refrain from pregnancy if of childbearing potential&#xD;
&#xD;
          -  Are unable to understand the investigational nature of the study or give informed&#xD;
             consent&#xD;
&#xD;
          -  Have a history of arterial or venous thrombosis within the last 1 year (excluding&#xD;
             those due to indwelling lines)&#xD;
&#xD;
          -  Have an ECOG performance status of 3 or greater&#xD;
&#xD;
          -  Have had treatment with Campath within 6 months of entry into the study&#xD;
&#xD;
          -  Have pre-existing cardiovascular disease (congestive heart failure with New York Heart&#xD;
             Association [NYHA] grade III/IV), arrhythmia known to increase the risk of&#xD;
             thromboembolic events (e.g. atrial fibrillation), unstable angina, or QTc &gt; 450 msec&#xD;
             (QTc 480 msec for subjects with bundle branch block), or myocardial infarction within&#xD;
             the preceding 6 months) at study entry&#xD;
&#xD;
          -  Have had other TPO-R agonists medication in the previous 4 weeks.&#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>George M Rodgers, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <results_first_submitted>June 16, 2017</results_first_submitted>
  <results_first_submitted_qc>September 12, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 19, 2017</results_first_posted>
  <last_update_submitted>September 12, 2017</last_update_submitted>
  <last_update_submitted_qc>September 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>severe aplastic anemia</keyword>
  <keyword>very severe aplastic anemia</keyword>
  <keyword>moderate aplastic anemia</keyword>
  <keyword>bleeding</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Eltrombopag</title>
          <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Eltrombopag</title>
          <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
          </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="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Count of Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants With Platelet Response</title>
        <description>Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.</description>
        <time_frame>up to 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Eltrombopag</title>
            <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Platelet Response</title>
          <description>Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.23" lower_limit="0.05" upper_limit="0.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <other_analysis_desc>The proportion of platelet response in a previous study (PMID:22762314) was 0.36 (9/25). The null hypothesis of no difference between the platelet response rate in this study and that of the previous study was tested using a two-sided exact test of binomial proportions. A p-value of 0.40 was obtained. The threshold for significance was 0.05.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Count Twice Baseline.</title>
        <description>Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.</description>
        <time_frame>Between weeks 1-12.</time_frame>
        <population>Data was not collected for this outcome variable.</population>
        <group_list>
          <group group_id="O1">
            <title>Eltrombopag</title>
            <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Count Twice Baseline.</title>
          <description>Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.</description>
          <population>Data was not collected for this outcome variable.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematology Labs</title>
        <description>Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia</description>
        <time_frame>12 weeks</time_frame>
        <population>Data was not collected for this outcome variable.</population>
        <group_list>
          <group group_id="O1">
            <title>Eltrombopag</title>
            <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
          </group>
        </group_list>
        <measure>
          <title>Hematology Labs</title>
          <description>Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia</description>
          <population>Data was not collected for this outcome variable.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With AE to Measure Toxicity, Using NCI CTCAE</title>
        <description>Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia</description>
        <time_frame>12 weeks</time_frame>
        <population>Data was not collected for this outcome variable.</population>
        <group_list>
          <group group_id="O1">
            <title>Eltrombopag</title>
            <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With AE to Measure Toxicity, Using NCI CTCAE</title>
          <description>Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia</description>
          <population>Data was not collected for this outcome variable.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.</title>
        <description>Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.</description>
        <time_frame>Weeks 2, 6 and 12</time_frame>
        <population>Data was not collected for this outcome variable.</population>
        <group_list>
          <group group_id="O1">
            <title>Eltrombopag</title>
            <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
          </group>
        </group_list>
        <measure>
          <title>Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.</title>
          <description>Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.</description>
          <population>Data was not collected for this outcome variable.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Approximately 3 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Eltrombopag</title>
          <description>Single arm study. Dose Escalation.&#xD;
Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>congestive heart failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="13" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>petechiae</sub_title>
                <counts group_id="E1" events="18" subjects_affected="11" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>transfusion reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>arrhythmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>opacity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>scleral icterus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>rectal hemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>aches/pains</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>night sweats</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>port leak</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>spelnomegaly</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>gum hypertrophy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>gum lesions</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>otitis externa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>bruising</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>decreased lymphocyte count</sub_title>
                <counts group_id="E1" events="22" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>decreased neutrophil count</sub_title>
                <counts group_id="E1" events="17" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>thrombocytopenia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="6" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>elevated ALT</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>elevated AST</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>elevated bilirubin</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>elevated creatinine</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hypoalbunemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>weight gain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hypocalcemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>cramps</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </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="13"/>
              </event>
              <event>
                <sub_title>dysgeusia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>sciatica</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </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="13"/>
              </event>
              <event>
                <sub_title>confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>pyelonephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>renal insufficiency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>menorrhagia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hypoxia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>shortness of breath</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>purpura</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>bronzing of the skin</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>dry skin</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>ecchymosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>facial hair growth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>jaundice</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>mouth sores</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>pallor</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>thrush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>hematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hot flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Certain data regarding the primary outcome and adverse events were inadvertently not captured during the clinical investigation resulting in insufficient data for statistical analysis and publication.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Kimberlee Taylor</name_or_title>
      <organization>Huntsman Cancer Institute</organization>
      <phone>8012135673</phone>
      <email>Kimberlee.Taylor@hci.utah.edu</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/NCT01703169
org study id: HCI54443
secondary id: ELT115895
nct id: NCT01703169
lead sponsor: 
collaborator: 
has dmc: Yes
The investigators hypothesis is that eltrombopag given to patients with moderate to very
      severe aplastic anemia will result in an increase in platelet counts. The investigators
      hypothesize that in patients with moderate to very severe aplastic anemia, treatment with
      eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer
      bleeding events. The investigators hypothesize that in patients with moderate to very severe
      aplastic anemia, eltrombopag will have an acceptable toxicity rate <3%, at doses that result
      in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag
      levels in peripheral blood will correlate with improved platelet counts.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Participants With Platelet Response
time frame: up to 12 weeks
description: Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.
measure: Platelet Count Twice Baseline.
time frame: Between weeks 1-12.
description: Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.
measure: Hematology Labs
time frame: 12 weeks
description: Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia
measure: Number of Patients With AE to Measure Toxicity, Using NCI CTCAE
time frame: 12 weeks
description: Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia
measure: Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.
time frame: Weeks 2, 6 and 12
description: Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.
arm group label: Eltrombopag
arm group type: Experimental
description: Single arm study. Dose Escalation.
intervention type: Drug
intervention name: Eltrombopag
description: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
arm group label: Eltrombopag
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: George M Rodgers, M.D.
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia
mesh term: Anemia, Aplastic
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Certain data regarding the primary outcome and adverse events were inadvertently not captured during the clinical investigation resulting in insufficient data for statistical analysis and publication.
point of contact: 