<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/NCT01682135</url>
  </required_header>
  <id_info>
    <org_study_id>14139</org_study_id>
    <secondary_id>I4T-CR-JVBU</secondary_id>
    <nct_id>NCT01682135</nct_id>
  </id_info>
  <brief_title>A Study in Participants With Advanced Solid Tumors</brief_title>
  <official_title>Phase I Study of Ramucirumab in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is testing ramucirumab (LY3009806) administered to Chinese participants with&#xD;
      advanced solid tumors that are resistant to standard therapy or for whom no standard therapy&#xD;
      is available. The purpose of this study is to evaluate how safe ramucirumab is and whether it&#xD;
      causes any side effects. The study will also measure how much ramucirumab gets into the blood&#xD;
      stream and how long it takes the body to get rid of it.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</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>Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline through Study Completion (Up to 12 Weeks)</time_frame>
    <description>A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab</measure>
    <time_frame>Cycle 1 &amp; 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab</measure>
    <time_frame>Cycle 2-5: Predose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab</measure>
    <time_frame>Cycle 1 &amp; 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)</time_frame>
    <description>Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC[0-∞]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC[τ,ss])</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)</time_frame>
    <description>Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Stable Disease (SD)</measure>
    <time_frame>Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)</time_frame>
    <description>Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Disease Progression</measure>
    <time_frame>Baseline to Progressive Disease (Up to 10 Weeks)</time_frame>
    <description>Time to progressive disease was measured from the start of study drug until progressive disease. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Ramucirumab Antibodies</measure>
    <time_frame>Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion</time_frame>
    <description>A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Best Objective Response (BOR)</measure>
    <time_frame>Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks)</time_frame>
    <description>Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Ramucirumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ramucirumab administered intravenously (IV) at escalating doses (6 milligrams per kilogram [mg/kg] up to 10 mg/kg) every 2-3 weeks for 6 weeks (1 Cycle). Treatment may continue until discontinuation criterion is met.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ramucirumab</intervention_name>
    <description>Administered IV.</description>
    <arm_group_label>Ramucirumab</arm_group_label>
    <other_name>IMC-1121B</other_name>
    <other_name>LY3009806</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chinese participants with histopathologically or cytologically diagnosed advanced&#xD;
             solid tumor&#xD;
&#xD;
          -  Did not respond to standard therapy or no standard therapy is available&#xD;
&#xD;
          -  Measurable or nonmeasurable disease according to the Response Evaluation Criteria In&#xD;
             Solid Tumors (RECIST)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 at study&#xD;
             entry&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
          -  A life expectancy of &gt;3 months&#xD;
&#xD;
          -  Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1500&#xD;
             per cubic millimeter (mm^3); hemoglobin concentration ≥9 grams per deciliter (g/dL);&#xD;
             and platelet count ≥100,000/mm^3&#xD;
&#xD;
          -  Adequate hepatic function, as defined by: Total bilirubin level ≤1.5 x the upper limit&#xD;
             of normal (ULN) (in participants with known Gilbert Syndrome, a total bilirubin ≤ 3.0&#xD;
             x ULN with direct bilirubin ≤ 1.5 x ULN); aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) ≤2.5 x ULN (or ≤5 x ULN if the participant has liver metastases&#xD;
&#xD;
          -  Adequate renal function, as defined by: Serum creatinine level ≤1.5 x ULN; or&#xD;
             calculated serum creatinine clearance (Cockcroft-Gault) ≥50 milliliters per minute&#xD;
             (mL/min)&#xD;
&#xD;
          -  Urinary protein is 0 or 1+ on dipstick but no edema nor serum albumin &lt; lower level of&#xD;
             normal&#xD;
&#xD;
          -  Adequate coagulation function, as defined by: International normalized ratio (INR)&#xD;
             ≤1.5, or prothrombin time (PT) ≤1.5 x ULN and activated partial thromboplastin time&#xD;
             (aPTT) ≤1.5 x ULN (unless receiving anticoagulation therapy)&#xD;
&#xD;
          -  Agrees to use adequate contraception during the study period and for 12 weeks after&#xD;
             the last dose of study treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Had chemotherapy or therapeutic radiotherapy within 14 days (6 weeks for nitrosoureas&#xD;
             or mitomycin C) before entering the study or the participant has ongoing side effects&#xD;
             (≥ Grade 2) due to previously administered agents&#xD;
&#xD;
          -  Has obvious evidence of intratumor cavitation&#xD;
&#xD;
          -  Has undergone major surgery within 28 days before study entry or has had a central&#xD;
             venous access device inserted within 7 days before study entry&#xD;
&#xD;
          -  Has a history of gastrointestinal perforation, postoperative bleeding complications,&#xD;
             or wound complications from a surgical procedure&#xD;
&#xD;
          -  Has elective or planned surgery to be conducted during the trial&#xD;
&#xD;
          -  Has documented and/or symptomatic brain or leptomeningeal metastases&#xD;
&#xD;
          -  Has uncontrolled ongoing illness, for example: thrombotic or hemorrhagic disorders;&#xD;
             hemoptysis; ongoing infection requiring systemic antibiotic treatment; congestive&#xD;
             heart failure, angina pectoris, angioplasty, stenting, or myocardial infarction within&#xD;
             6 months; stroke, transient ischemic attack (TIA), or other grade 3-4 arterial&#xD;
             thromboembolic event occurring within 6 months; uncontrolled hypertension (≥150/≥90&#xD;
             millimeters of mercury [mmHg]); cardiac arrhythmia that requires treatment or&#xD;
             asymptomatic sustained ventricular tachycardia; peripheral neuropathy ≥Grade 2; human&#xD;
             immunodeficiency virus (HIV) or active, uncontrolled hepatitis, liver cirrhosis at a&#xD;
             level of Child-Pugh Class B (or worse), liver cirrhosis (any degree) and a history of&#xD;
             hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.&#xD;
             (Clinically meaningful ascites is defined as ascites resulting from cirrhosis and&#xD;
             requiring ongoing treatment with diuretics and/or paracentesis)&#xD;
&#xD;
          -  Has a serious or nonhealing wound, ulcer, or bone fracture within 28 days before study&#xD;
             entry&#xD;
&#xD;
          -  Has experienced any Grade 3 or 4 gastrointestinal bleeding within 3 months before&#xD;
             study entry&#xD;
&#xD;
          -  Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal&#xD;
             abscess &lt;6 months before randomization, or the participant has a history of poorly&#xD;
             controlled or recurrent inflammatory bowel disease (including Crohn's disease or&#xD;
             ulcerative colitis)&#xD;
&#xD;
          -  Has participated in a clinical study of a non-approved experimental agent or procedure&#xD;
             within 4 weeks prior to study entry for small molecules, or 8 weeks before study entry&#xD;
             for non-approved monoclonal antibodies&#xD;
&#xD;
          -  Has a known allergy to ramucirumab or its excipients, a monoclonal antibody (MAb), or&#xD;
             any other therapeutic protein, such as fresh frozen plasma, human serum albumin (HSA),&#xD;
             cytokines, or interleukins. If there is suspicion that the participant may have an&#xD;
             allergy, the participant should be excluded&#xD;
&#xD;
          -  Is pregnant (confirmed by urine or serum pregnancy test) or lactating&#xD;
&#xD;
          -  Has known alcohol or drug dependency&#xD;
&#xD;
          -  Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs)&#xD;
&#xD;
          -  Is not considered to be suitable for this study, in the opinion of the investigator&#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>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>March 14, 2016</results_first_submitted>
  <results_first_submitted_qc>July 15, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 26, 2016</results_first_posted>
  <last_update_submitted>July 15, 2016</last_update_submitted>
  <last_update_submitted_qc>July 15, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ramucirumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participant study completion is defined as a participant either completing all 6 cycles of study drug or discontinuing study drug due to dose-limiting toxicities (DLT), then completing all required End-of-Therapy and End-of-Study assessments.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 - 6 mg/kg/2w Ramucirumab</title>
          <description>6 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2. After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2 - 10 mg/kg/3w Ramucirumab</title>
          <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3. After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3 - 8 mg/kg/2w Ramucirumab</title>
          <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). After Cycle 1 treatment, participants who had an objective response or stable disease were permitted to receive ramucirumab at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1 - 6 mg/kg/2w Ramucirumab</title>
          <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle) followed by dose escalation to Cohort 2. When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2 - 10 mg/kg/3w Ramucirumab</title>
          <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle) followed by dose escalation to Cohort 3. When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 3 - 8 mg/kg/2w Ramucirumab</title>
          <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.20" spread="9.060"/>
                    <measurement group_id="B2" value="52.92" spread="9.509"/>
                    <measurement group_id="B3" value="58.18" spread="9.444"/>
                    <measurement group_id="B4" value="54.80" spread="9.536"/>
                  </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="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)</title>
        <description>A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.</description>
        <time_frame>Baseline through Study Completion (Up to 12 Weeks)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered intravenously (IV) every 2 weeks (w) for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)</title>
          <description>A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.</description>
          <population>All enrolled participants who received at least one dose of study drug.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Drug-Related Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab</title>
        <time_frame>Cycle 1 &amp; 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug and had evaluable Cmax pharmacokinetics (PK) data.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab</title>
          <population>All enrolled participants who received at least one dose of study drug and had evaluable Cmax pharmacokinetics (PK) data.</population>
          <units>microgram/milliliter (µg/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 (n = 6, 9, 12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="155" spread="13"/>
                    <measurement group_id="O2" value="186" spread="22"/>
                    <measurement group_id="O3" value="190" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 (n = 1, 6, 8)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Geometric Mean and %CV not calculated for 1 participant. Individual Value = 155 µg/mL.</measurement>
                    <measurement group_id="O2" value="219" spread="22"/>
                    <measurement group_id="O3" value="239" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab</title>
        <time_frame>Cycle 2-5: Predose</time_frame>
        <population>All enrolled participants who received at least one dose of study drug and had evaluable Cmin PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab</title>
          <population>All enrolled participants who received at least one dose of study drug and had evaluable Cmin PK data.</population>
          <units>µg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 (n = 5, 8, 10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.9" spread="35"/>
                    <measurement group_id="O2" value="29.5" spread="90"/>
                    <measurement group_id="O3" value="59.7" spread="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 (n = 1, 2, 5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Geometric Mean and %CV not calculated for 1 participant. Individual Value = 37.1 µg/mL.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Geometric Mean and %CV not calculated for 2 participants. Individual Values = 41.2 and 50.2 µg/mL.</measurement>
                    <measurement group_id="O3" value="68.7" spread="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (n = 1, 2, 4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Geometric Mean and %CV not calculated for 1 participant. Individual Value = 51.9 µg/mL.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Geometric Mean and %CV not calculated for 2 participants. Individual Values = 56.0 and 84.1 µg/mL.</measurement>
                    <measurement group_id="O3" value="79.6" spread="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5 (n = 0, 3, 4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Geometric Mean and %CV not calculated for 0 participants; no data.</measurement>
                    <measurement group_id="O2" value="56.5" spread="17"/>
                    <measurement group_id="O3" value="92.5" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab</title>
        <description>Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC[0-∞]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC[τ,ss])</description>
        <time_frame>Cycle 1 &amp; 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug and had evaluable AUC(0-∞) for Cycle 1 and AUC(τ,ss) for Cycle 2 PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab</title>
          <description>Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC[0-∞]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC[τ,ss])</description>
          <population>All enrolled participants who received at least one dose of study drug and had evaluable AUC(0-∞) for Cycle 1 and AUC(τ,ss) for Cycle 2 PK data.</population>
          <units>Microgram*day/milliliter (µg*day/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 AUC(0-∞) (n = 5, 7, 7)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="870" spread="14"/>
                    <measurement group_id="O2" value="1430" spread="31"/>
                    <measurement group_id="O3" value="1350" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 AUC(τ,ss) (n = 1, 6, 8)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Geometric Mean and %CV not calculated for 1 participant. Mean Value = 892 µg*day/mL).</measurement>
                    <measurement group_id="O2" value="1630" spread="32"/>
                    <measurement group_id="O3" value="1540" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.</description>
        <time_frame>Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug. There were no participants censored due to no CR or PR responses.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.</description>
          <population>All enrolled participants who received at least one dose of study drug. There were no participants censored due to no CR or PR responses.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Stable Disease (SD)</title>
        <description>Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
        <time_frame>Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug and had evaluable SD data. Participants censored for Cohort 1, 2, and 3: 3, 2, and 1, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Stable Disease (SD)</title>
          <description>Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
          <population>All enrolled participants who received at least one dose of study drug and had evaluable SD data. Participants censored for Cohort 1, 2, and 3: 3, 2, and 1, respectively.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">The number of values in this cohort was too small to calculate due to censoring.</measurement>
                    <measurement group_id="O2" value="5.68" lower_limit="2.79" upper_limit="12.22"/>
                    <measurement group_id="O3" value="5.29" lower_limit="2.92" upper_limit="6.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Disease Progression</title>
        <description>Time to progressive disease was measured from the start of study drug until progressive disease. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
        <time_frame>Baseline to Progressive Disease (Up to 10 Weeks)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug. Censoring for Cohort 1, 2 and 3: 3, 2 and 2, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Disease Progression</title>
          <description>Time to progressive disease was measured from the start of study drug until progressive disease. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.</description>
          <population>All enrolled participants who received at least one dose of study drug. Censoring for Cohort 1, 2 and 3: 3, 2 and 2, respectively.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.41" lower_limit="1.35" upper_limit="NA">The number of values in this cohort was too small to calculate due to censoring.</measurement>
                    <measurement group_id="O2" value="3.38" lower_limit="1.28" upper_limit="8.21"/>
                    <measurement group_id="O3" value="3.94" lower_limit="1.22" upper_limit="5.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-Ramucirumab Antibodies</title>
        <description>A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive.</description>
        <time_frame>Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion</time_frame>
        <population>All enrolled participants who received at least one dose of study drug and had evaluable immunogenicity data.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Ramucirumab Antibodies</title>
          <description>A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive.</description>
          <population>All enrolled participants who received at least one dose of study drug and had evaluable immunogenicity data.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Best Objective Response (BOR)</title>
        <description>Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.</description>
        <time_frame>Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks)</time_frame>
        <population>All enrolled participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: 6 mg/kg/2w Ramucirumab</title>
            <description>6 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: 10 mg/kg/3w Ramucirumab</title>
            <description>10 mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3: 8 mg/kg/2w Ramucirumab</title>
            <description>8 mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Best Objective Response (BOR)</title>
          <description>Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to &lt;10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.</description>
          <population>All enrolled participants who received at least one dose of study drug.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response (CR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease (PD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable (NE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1 - 6mg/kg/2w Ramucirumab</title>
          <description>6mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 2.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2 - 10mg/kg/3w Ramucirumab</title>
          <description>10mg/kg ramucirumab administered IV every 3 weeks for 6 weeks (one cycle). When a pre-defined percentage of participants completed Cycle 1 without experiencing a DLT, dose escalation was initiated with the start of Cohort 3.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 3 - 8mg/kg/2w Ramucirumab</title>
          <description>8mg/kg ramucirumab administered IV every 2 weeks for 6 weeks (one cycle).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</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="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 17.1</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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="12"/>
              </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="4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Extrasystoles</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="27" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="10" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Ventricular arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="8" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oral dysaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="11" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </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="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E3" events="11" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E3" events="13" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram st segment abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram t wave abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Glucose urine present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White blood cells urine positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </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="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Haemangioma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="8" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Renal failure chronic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menstruation irregular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pulmonary haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nail discolouration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="29" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E3" events="14" subjects_affected="5" subjects_at_risk="12"/>
              </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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Eli Lilly and Company</organization>
      <phone>800-545-5979</phone>
    </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/NCT01682135
org study id: 14139
secondary id: I4T-CR-JVBU
nct id: NCT01682135
lead sponsor: 
has dmc: No
This trial is testing ramucirumab (LY3009806) administered to Chinese participants with
      advanced solid tumors that are resistant to standard therapy or for whom no standard therapy
      is available. The purpose of this study is to evaluate how safe ramucirumab is and whether it
      causes any side effects. The study will also measure how much ramucirumab gets into the blood
      stream and how long it takes the body to get rid of it.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
time frame: Baseline through Study Completion (Up to 12 Weeks)
description: A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
time frame: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
measure: Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
time frame: Cycle 2-5: Predose
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
time frame: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
description: Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC[0-∞]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC[τ,ss])
measure: Duration of Response
time frame: Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)
description: Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.
measure: Duration of Stable Disease (SD)
time frame: Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks)
description: Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.
measure: Time to Disease Progression
time frame: Baseline to Progressive Disease (Up to 10 Weeks)
description: Time to progressive disease was measured from the start of study drug until progressive disease. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.
measure: Number of Participants With Anti-Ramucirumab Antibodies
time frame: Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion
description: A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive.
measure: Number of Participants With Best Objective Response (BOR)
time frame: Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks)
description: Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.
arm group label: Ramucirumab
arm group type: Experimental
description: Ramucirumab administered intravenously (IV) at escalating doses (6 milligrams per kilogram [mg/kg] up to 10 mg/kg) every 2-3 weeks for 6 weeks (1 Cycle). Treatment may continue until discontinuation criterion is met.
intervention type: Biological
intervention name: Ramucirumab
description: Administered IV.
arm group label: Ramucirumab
other name: IMC-1121B
other name: LY3009806
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Ramucirumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 