<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/NCT01663857</url>
  </required_header>
  <id_info>
    <org_study_id>12517</org_study_id>
    <secondary_id>I1D-MC-JIAE</secondary_id>
    <nct_id>NCT01663857</nct_id>
  </id_info>
  <brief_title>A Study LY2228820 for Recurrent Ovarian Cancer</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer</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>
      A study for women with ovarian cancer that has returned at least 6 months after&#xD;
      platinum-based chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase 1b is unblinded and will have a small number of participants that will take LY2228820&#xD;
      plus gemcitabine and carboplatin to test the safety of the combination and determine a&#xD;
      recommended dose for the Phase 2 portion.&#xD;
&#xD;
      Phase 2 will be blinded and all study participants will receive carboplatin and gemcitabine.&#xD;
      Participants of one group will receive LY2228820, and the other group will receive placebo.&#xD;
&#xD;
      If the participant achieves at least stable disease, there is a maintenance phase following&#xD;
      the first 6 cycles. The participant will take either LY2228820 or placebo. The participant&#xD;
      will continue therapy until disease progression or other discontinuation criteria are&#xD;
      fulfilled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">May 11, 2018</completion_date>
  <primary_completion_date type="Actual">May 25, 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])</measure>
    <time_frame>Cycle 1 (21 Days)</time_frame>
    <description>Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin</measure>
    <time_frame>Randomization to Date of Disease Progression or Death from any cause (up to 3 years)</time_frame>
    <description>PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)</measure>
    <time_frame>Baseline to Disease Progression (up to 3 years)</time_frame>
    <description>Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Overall Survival</measure>
    <time_frame>Baseline to Date of Death from any cause (up to 5 years)</time_frame>
    <description>Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820</measure>
    <time_frame>Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD</time_frame>
    <description>PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score</measure>
    <time_frame>Baseline, Study Completion (up to 3 years)</time_frame>
    <description>The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = &quot;not at all&quot; and 4 = &quot;very much.&quot; Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">118</enrollment>
  <condition>Epithelial Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Primary Peritoneal Cancer</condition>
  <arm_group>
    <arm_group_label>Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3..&#xD;
Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1b (Cohort 2) LY2228820 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.&#xD;
Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 (Arm A) LY2228820 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.&#xD;
Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 (Arm B) Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Arm B: Cycles 1-6 (21 day cycles)- Placebo administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.&#xD;
Arm B: Cycle 7+ (28 day cycles)- Placebo administered orally on days 1-14 to maintain blind.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2228820</intervention_name>
    <description>Administered Orally</description>
    <arm_group_label>Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)</arm_group_label>
    <arm_group_label>Phase 1b (Cohort 2) LY2228820 300 mg</arm_group_label>
    <arm_group_label>Phase 2 (Arm A) LY2228820 200 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)</arm_group_label>
    <arm_group_label>Phase 1b (Cohort 2) LY2228820 300 mg</arm_group_label>
    <arm_group_label>Phase 2 (Arm A) LY2228820 200 mg</arm_group_label>
    <arm_group_label>Phase 2 (Arm B) Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered Orally</description>
    <arm_group_label>Phase 2 (Arm B) Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)</arm_group_label>
    <arm_group_label>Phase 1b (Cohort 2) LY2228820 300 mg</arm_group_label>
    <arm_group_label>Phase 2 (Arm A) LY2228820 200 mg</arm_group_label>
    <arm_group_label>Phase 2 (Arm B) Placebo</arm_group_label>
    <other_name>Gemzar</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have been diagnosed with ovarian, fallopian tube, or primary peritoneal cancer&#xD;
&#xD;
          -  Have been treated one time with a platinum-based chemotherapy and your disease has&#xD;
             come back at least six months after you completed treatment&#xD;
&#xD;
          -  Are able to swallow tablets&#xD;
&#xD;
          -  Have given written informed consent prior to any study procedures&#xD;
&#xD;
          -  Have adequate blood counts, hepatic and renal function&#xD;
&#xD;
          -  Have performance status equal to or less than 2 on Eastern Cooperative Oncology Group&#xD;
             (ECOG) scale&#xD;
&#xD;
          -  Have negative pregnancy test, and if participant is of child bearing potential must&#xD;
             use birth control while on study and for three months after stopping study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have been previously treated with Gemcitabine for ovarian, fallopian tube or primary&#xD;
             peritoneal cancer&#xD;
&#xD;
          -  Are currently enrolled or discontinued less than 14 days from another clinical trial&#xD;
&#xD;
          -  Have a history of inflammatory bowel disease (Crohn's disease or ulcerative colitis)&#xD;
&#xD;
          -  Have taken certain medications or had grapefruit juice within 7 days of initial dose&#xD;
             of study drug, as levels of the study drug may be affected.&#xD;
&#xD;
          -  Must not be pregnant or breastfeeding.&#xD;
&#xD;
          -  Have malignancy or metastasis of the central nervous system&#xD;
&#xD;
          -  Have borderline malignancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</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 9am-5pm Eastern time *UTC/GMT-5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Josephs Hospital and Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates, P.C.</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarasota Memorial Hospital</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franklin Square Hospital Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barnes Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SMO Sarah Cannon Research Inst.</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Bedford</city>
        <state>Texas</state>
        <zip>76022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Centers of South Texas</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - The Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Oncology</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tyler Cancer Center</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists PC</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Adelaide</city>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <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>Greenslopes</city>
        <zip>4120</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <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>Nedlands</city>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <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>Parkville</city>
        <zip>3053</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <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>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <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>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <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>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <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>Essen</city>
        <zip>45136</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <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>Greifswald</city>
        <zip>17489</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <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>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <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>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>India</country>
  </removed_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>May 8, 2019</results_first_submitted>
  <results_first_submitted_qc>May 8, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 29, 2019</results_first_posted>
  <disposition_first_submitted>May 4, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>May 4, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 8, 2018</disposition_first_posted>
  <last_update_submitted>August 28, 2019</last_update_submitted>
  <last_update_submitted_qc>August 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2019</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>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.</ipd_time_frame>
    <ipd_access_criteria>A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT01663857/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT01663857/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants in Phase 1b are considered to have completed the study if they experience a dose-limiting toxicity or completed the Pharmacokinetic (PK) sampling set. Participants in Phase 2 are considered to have completed if they die due to any cause or who are alive and on study at conclusion, but are off treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6).&#xD;
Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).</description>
        </group>
        <group group_id="P2">
          <title>Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).</description>
        </group>
        <group group_id="P3">
          <title>Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
        </group>
        <group group_id="P4">
          <title>Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin</title>
          <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</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="2"/>
                <participants group_id="P3" count="58"/>
                <participants group_id="P4" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least One Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="58"/>
                <participants group_id="P4" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="48"/>
                <participants group_id="P4" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrew Consent to Study Participation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Phase 1b: Cohort 1: LY2228820 +Gemcitabine+Carboplatin</title>
          <description>Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6).&#xD;
Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10.&#xD;
Carboplatin area under the concentration curve administered intravenously (IV) over 30 minutes (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3.&#xD;
Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).</description>
        </group>
        <group group_id="B2">
          <title>Phase 1b: Cohort 2: LY2228820 +Gemcitabine+Carboplatin</title>
          <description>Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).&#xD;
Gemcitabine 1000 mg/m2 administered IV over 30 min on Days 3 and 10.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.&#xD;
Cohort 2:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).</description>
        </group>
        <group group_id="B3">
          <title>Arm A: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Arm A:LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.&#xD;
Arm A:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).</description>
        </group>
        <group group_id="B4">
          <title>Arm B Placebo + Gemcitabine +Carboplatin</title>
          <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle (Cycles 1-6).&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).</description>
        </group>
        <group group_id="B5">
          <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="2"/>
            <count group_id="B3" value="58"/>
            <count group_id="B4" value="52"/>
            <count group_id="B5" value="118"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.7" spread="6.8"/>
                    <measurement group_id="B2" value="65.0" spread="5.7"/>
                    <measurement group_id="B3" value="60.9" spread="10.4"/>
                    <measurement group_id="B4" value="62.2" spread="9.2"/>
                    <measurement group_id="B5" value="61.6" spread="9.6"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="58"/>
                    <measurement group_id="B4" value="52"/>
                    <measurement group_id="B5" value="118"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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 group_id="B5" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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 group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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="2"/>
                    <measurement group_id="B5" value="2"/>
                  </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 group_id="B5" 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="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="57"/>
                    <measurement group_id="B4" value="49"/>
                    <measurement group_id="B5" value="113"/>
                  </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 group_id="B5" 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="1"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Belgium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="25"/>
                    <measurement group_id="B5" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="2"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Maintenance Therapy as a Part of or After a First Line Platinum Regimen</title>
          <population>Maintenance therapy as part of or after first line platinum regimen data was used as a cofactor in the analysis of Progression Free Survival (PFS). Zero participants analyzed for Phase 1 portion of the study.Data was collected only from participants treated in the Phase 2 portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Received Maintenance Therapy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Did Not Receive Maintenance Therapy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Data Missing or Not Collected</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="58"/>
                    <count group_id="B4" value="52"/>
                    <count group_id="B5" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])</title>
        <description>Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).</description>
        <time_frame>Cycle 1 (21 Days)</time_frame>
        <population>All participants who received at least one dose of study drug in Phase 1b.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2228820 + Gemcitabine + Carboplatin</title>
            <description>Cohort 1 : LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6)&#xD;
Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10&#xD;
Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Cohort 1 and 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])</title>
          <description>Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).</description>
          <population>All participants who received at least one dose of study drug in Phase 1b.</population>
          <units>milligrams (mg)</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin</title>
        <description>PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
        <time_frame>Randomization to Date of Disease Progression or Death from any cause (up to 3 years)</time_frame>
        <population>All participants in Phase 2 who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2228820 + Gemcitabine +Carboplatin</title>
            <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of 21-day cycles.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of 21-day cycles.&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Gemcitabine + Carboplatin</title>
            <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of 21-day cycles.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. n Day 3 of 21-day cycles.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin</title>
          <description>PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.</description>
          <population>All participants in Phase 2 who received at least one dose of study drug.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.25" lower_limit="7.85" upper_limit="10.87"/>
                    <measurement group_id="O2" value="8.44" lower_limit="7.56" upper_limit="9.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)</title>
        <description>Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.</description>
        <time_frame>Baseline to Disease Progression (up to 3 years)</time_frame>
        <population>All participants who received at least one dose of study drug in Phase 2.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2228820 + Gemcitabine +Carboplatin</title>
            <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min.(+ 15 min.) on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Gemcitabine + Carboplatin</title>
            <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)</title>
          <description>Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.</description>
          <population>All participants who received at least one dose of study drug in Phase 2.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.6"/>
                    <measurement group_id="O2" value="46.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Overall Survival</title>
        <description>Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.</description>
        <time_frame>Baseline to Date of Death from any cause (up to 5 years)</time_frame>
        <population>All participants in Phase 2 who received at least one dose of drug.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2228820 + Gemcitabine +Carboplatin</title>
            <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Gemcitabine + Carboplatin</title>
            <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Overall Survival</title>
          <description>Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.</description>
          <population>All participants in Phase 2 who received at least one dose of drug.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.17" lower_limit="23.26" upper_limit="52.40"/>
                    <measurement group_id="O2" value="25.10" lower_limit="21.95" upper_limit="33.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4686</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820</title>
        <description>PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.</description>
        <time_frame>Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD</time_frame>
        <population>All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>200 mg LY2228820</title>
            <description>Phase 1b (Cohort 1) and Phase 2 (Arm A): LY2228820 200 mg administered orally every 12 hours on Days 1-10, Cycles 1-6 of a 21 day cycle.&#xD;
.</description>
          </group>
          <group group_id="O2">
            <title>300 mg LY2228820</title>
            <description>Phase 1b (Cohort 2) and Phase 2 (Arm A) in the maintenance portion with LY2228820 300 mg administered orally every 12 hours on Days 1-14 Cycle 7+ of a 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820</title>
          <description>PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.</description>
          <population>All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.</population>
          <units>nanograms * hr per milliliter (ng*hr/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="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3470" spread="91"/>
                    <measurement group_id="O2" value="3560" spread="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3170" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4270" spread="62"/>
                    <measurement group_id="O2" value="9350" spread="NA">Due to n of 1 individual value provided.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3270" spread="38"/>
                    <measurement group_id="O2" value="3490" spread="NA">Due to n of 1 individual value provided.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 7 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="7230" spread="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score</title>
        <description>The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = &quot;not at all&quot; and 4 = &quot;very much.&quot; Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.</description>
        <time_frame>Baseline, Study Completion (up to 3 years)</time_frame>
        <population>All participants in Phase 2 who received at least one dose of study drug and had at least one post baseline assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2228820 + Gemcitabine +Carboplatin</title>
            <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day.&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Gemcitabine + Carboplatin</title>
            <description>Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle.&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle.&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle.&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score</title>
          <description>The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = &quot;not at all&quot; and 4 = &quot;very much.&quot; Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.</description>
          <population>All participants in Phase 2 who received at least one dose of study drug and had at least one post baseline assessment.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="21.14"/>
                    <measurement group_id="O2" value="-8.9" spread="19.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 4.5 years</time_frame>
      <desc>All participants who received at least one dose of drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Cohort 1: LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6)&#xD;
Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10&#xD;
Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
        </group>
        <group group_id="E2">
          <title>Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
        </group>
        <group group_id="E3">
          <title>Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin</title>
          <description>Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
        </group>
        <group group_id="E4">
          <title>Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin</title>
          <description>Arm B: Placebo orally every 12 hrs. on Days 1-10&#xD;
Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10&#xD;
Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3&#xD;
Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="58"/>
                <counts group_id="E4" subjects_affected="31" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="58"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Leukopenia</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Neutropenia</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</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="2"/>
                <counts group_id="E3" events="7" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Abdominal 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="2"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Ascites</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Constipation</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diarrhoea</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Ileus</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nausea</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Subileus</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Vomiting</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="2"/>
                <counts group_id="E3" events="6" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General physical health deterioration</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Malaise</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pyrexia</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Appendicitis</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Bacteraemia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Erysipelas</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Lung infection</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pelvic infection</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pneumonia</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sepsis</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Ureteritis</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Cervical vertebral fracture</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fall</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Thermal burn</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urostomy complication</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase 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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase 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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nuclear magnetic resonance imaging abdominal abnormal</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Platelet 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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flank 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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Joint effusion</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Headache</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Presyncope</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Syncope</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pneumonitis</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug reaction with eosinophilia and systemic symptoms</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</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="2" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="58" subjects_at_risk="58"/>
                <counts group_id="E4" subjects_affected="52" subjects_at_risk="52"/>
              </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="8" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="91" subjects_affected="32" subjects_at_risk="58"/>
                <counts group_id="E4" events="73" subjects_affected="25" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Increased tendency to bruise</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Leukocytosis</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="2"/>
                <counts group_id="E3" events="8" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Leukopenia</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" events="72" subjects_affected="26" subjects_at_risk="58"/>
                <counts group_id="E4" events="74" subjects_affected="26" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="40" subjects_affected="17" subjects_at_risk="58"/>
                <counts group_id="E4" events="47" subjects_affected="14" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</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="2"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E4" events="9" subjects_affected="8" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</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="2"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Vertigo</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Glaucoma</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Visual impairment</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <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="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E4" events="13" subjects_affected="12" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Abdominal 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="2"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="58"/>
                <counts group_id="E4" events="9" subjects_affected="8" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Anal incontinence</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="31" subjects_affected="23" subjects_at_risk="58"/>
                <counts group_id="E4" events="24" subjects_affected="22" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="40" subjects_affected="23" subjects_at_risk="58"/>
                <counts group_id="E4" events="18" subjects_affected="14" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dyspepsia</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dysphagia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="39" subjects_affected="31" subjects_at_risk="58"/>
                <counts group_id="E4" events="50" subjects_affected="33" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rectal 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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="10" subjects_affected="9" subjects_at_risk="58"/>
                <counts group_id="E4" events="11" subjects_affected="10" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="23" subjects_affected="17" subjects_at_risk="58"/>
                <counts group_id="E4" events="12" subjects_affected="12" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="50" subjects_affected="40" subjects_at_risk="58"/>
                <counts group_id="E4" events="48" subjects_affected="38" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</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="2"/>
                <counts group_id="E3" events="9" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="8" subjects_affected="7" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pyrexia</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="2"/>
                <counts group_id="E3" events="9" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="6" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</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="2"/>
                <counts group_id="E3" events="7" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Cystitis</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pneumonia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</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="2"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</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="2"/>
                <counts group_id="E3" events="14" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E4" events="10" subjects_affected="7" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="8" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="11" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Wrist fracture</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="42" subjects_affected="25" subjects_at_risk="58"/>
                <counts group_id="E4" events="35" subjects_affected="13" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="28" subjects_affected="17" subjects_at_risk="58"/>
                <counts group_id="E4" events="22" subjects_affected="10" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</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="2"/>
                <counts group_id="E3" events="12" subjects_affected="9" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="7" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Blood urea 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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Haemoglobin 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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Lymphocyte 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="2"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</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="2"/>
                <counts group_id="E3" events="76" subjects_affected="26" subjects_at_risk="58"/>
                <counts group_id="E4" events="92" subjects_affected="29" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="53" subjects_affected="21" subjects_at_risk="58"/>
                <counts group_id="E4" events="66" subjects_affected="20" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Weight 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="2"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="47" subjects_affected="20" subjects_at_risk="58"/>
                <counts group_id="E4" events="55" subjects_affected="19" subjects_at_risk="52"/>
              </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="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="15" subjects_affected="14" subjects_at_risk="58"/>
                <counts group_id="E4" events="13" subjects_affected="12" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dehydration</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</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="2"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </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="2"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</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="2"/>
                <counts group_id="E3" events="11" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="14" subjects_affected="5" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="10" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="13" subjects_affected="12" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Bone 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="2"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Flank 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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Muscle spasms</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="2"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myalgia</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="6" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Neck 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="2"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Osteopenia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pain in extremity</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="2"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</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="2"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="58"/>
                <counts group_id="E4" events="9" subjects_affected="9" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dysgeusia</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="58"/>
                <counts group_id="E4" events="20" subjects_affected="12" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Paraesthesia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Syncope</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Tremor</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="2"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Adjustment disorder with depressed mood</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Anxiety</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Insomnia</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pollakiuria</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal discharge</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pruritus</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </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="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="11" subjects_affected="11" subjects_at_risk="58"/>
                <counts group_id="E4" events="12" subjects_affected="12" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dyspnoea</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="2"/>
                <counts group_id="E3" events="20" subjects_affected="17" subjects_at_risk="58"/>
                <counts group_id="E4" events="10" subjects_affected="9" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Epistaxis</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="2"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypoxia</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nasal congestion</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="2"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Oropharyngeal 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="2"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Paranasal sinus discomfort</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Productive cough</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="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</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="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</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="2"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="58"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Dry skin</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pruritus</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="2"/>
                <counts group_id="E3" events="10" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rash</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="2"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E4" events="6" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Social problem</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</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="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Hypertension</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="2"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </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>800-575-5979</phone>
      <email>Clinicaltrials.gov@lilly.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01663857
org study id: 12517
secondary id: I1D-MC-JIAE
nct id: NCT01663857
lead sponsor: 
has dmc: No
A study for women with ovarian cancer that has returned at least 6 months after
      platinum-based chemotherapy.
Phase 1b is unblinded and will have a small number of participants that will take LY2228820
      plus gemcitabine and carboplatin to test the safety of the combination and determine a
      recommended dose for the Phase 2 portion.

      Phase 2 will be blinded and all study participants will receive carboplatin and gemcitabine.
      Participants of one group will receive LY2228820, and the other group will receive placebo.

      If the participant achieves at least stable disease, there is a maintenance phase following
      the first 6 cycles. The participant will take either LY2228820 or placebo. The participant
      will continue therapy until disease progression or other discontinuation criteria are
      fulfilled.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])
time frame: Cycle 1 (21 Days)
description: Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).
measure: Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin
time frame: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)
description: PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
measure: Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)
time frame: Baseline to Disease Progression (up to 3 years)
description: Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.
measure: Phase 2: Overall Survival
time frame: Baseline to Date of Death from any cause (up to 5 years)
description: Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.
measure: Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820
time frame: Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD
description: PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.
measure: Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score
time frame: Baseline, Study Completion (up to 3 years)
description: The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.
arm group label: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)
arm group type: Experimental
description: Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3..
Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.
arm group label: Phase 1b (Cohort 2) LY2228820 300 mg
arm group type: Experimental
description: Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.
Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.
arm group label: Phase 2 (Arm A) LY2228820 200 mg
arm group type: Experimental
description: Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.
Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.
arm group label: Phase 2 (Arm B) Placebo
arm group type: Placebo Comparator
description: Arm B: Cycles 1-6 (21 day cycles)- Placebo administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.
Arm B: Cycle 7+ (28 day cycles)- Placebo administered orally on days 1-14 to maintain blind.
intervention type: Drug
intervention name: LY2228820
description: Administered Orally
arm group label: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)
arm group label: Phase 1b (Cohort 2) LY2228820 300 mg
arm group label: Phase 2 (Arm A) LY2228820 200 mg
intervention type: Drug
intervention name: Carboplatin
description: Administered IV
arm group label: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)
arm group label: Phase 1b (Cohort 2) LY2228820 300 mg
arm group label: Phase 2 (Arm A) LY2228820 200 mg
arm group label: Phase 2 (Arm B) Placebo
intervention type: Drug
intervention name: Placebo
description: Administered Orally
arm group label: Phase 2 (Arm B) Placebo
intervention type: Drug
intervention name: Gemcitabine
description: Administered IV
arm group label: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)
arm group label: Phase 1b (Cohort 2) LY2228820 300 mg
arm group label: Phase 2 (Arm A) LY2228820 200 mg
arm group label: Phase 2 (Arm B) Placebo
other name: Gemzar
other name: LY188011
criteria: 
gender: Female
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 9am-5pm Eastern time *UTC/GMT-5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
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country: Australia
country: Belgium
country: Germany
country: United States
country: India
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Fallopian Tube Neoplasms
mesh term: Carboplatin
mesh term: Gemcitabine
sharing ipd: Yes
ipd description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
ipd access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
ipd url: https://vivli.org/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 