<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/NCT02186301</url>
  </required_header>
  <id_info>
    <org_study_id>CO-1686-022 (TIGER-1)</org_study_id>
    <nct_id>NCT02186301</nct_id>
  </id_info>
  <brief_title>TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy</brief_title>
  <acronym>EGFR</acronym>
  <official_title>TIGER 1: A Randomized, Open-Label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients With EGFR-Mutant Advanced/Metastatic NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clovis Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clovis Oncology, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with&#xD;
      erlotinib in patients whose tumors have specific EGFR mutations and who have not previously&#xD;
      received any treatment for advanced/metastatic EGFR mutated NSCLC. This study is a&#xD;
      'Randomized' Study. This means that upon entering the study, patients will be randomly&#xD;
      assigned to be dosed with either rociletinib twice a day or erlotinib once a day. Patients&#xD;
      will continue to take either rociletinib or erlotinib until it is no longer beneficial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line&#xD;
      treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have&#xD;
      EGFR-activating mutations. The study will consist of Phase 2 and Phase 3 parts which will use&#xD;
      the same enrollment criteria and treatment assignment principles. Patients will be randomized&#xD;
      1:1 to erlotinib or rociletinib. The Phase 2 part is an open-label study. In the Phase 3&#xD;
      part, the sponsor will be blinded to the efficacy and safety results. The study will consist&#xD;
      of a screening phase to establish study eligibility (including tumor genotype) and document&#xD;
      baseline measurements, a treatment phase, in which patients will receive either rociletinib&#xD;
      BID (twice a day) or erlotinib QD (once daily) to ascertain safety and efficacy until&#xD;
      protocol-defined disease progression, and a follow-up phase, to monitor survival status and&#xD;
      subsequent NSCLC cancer therapy. In the Phase 2 part only, patients initially randomized to&#xD;
      erlotinib may be eligible to participate in an optional crossover phase to receive&#xD;
      rociletinib if they demonstrate the T790M resistance mutation after radiographic progression&#xD;
      on erlotinib treatment among other eligibility requirements. Patients eligible for this study&#xD;
      must have EGFR-mutated NSCLC who have not been treated with an EGFR-directed&#xD;
      therapy.Treatment with rociletinib or erlotinib is continuous. Each 28 day period of&#xD;
      treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor discontinued development of CO-1686 for NSCLC&#xD;
  </why_stopped>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">June 28, 2017</completion_date>
  <primary_completion_date type="Actual">June 28, 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)</measure>
    <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months</time_frame>
    <description>To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Confirmed Response Rate</measure>
    <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.</time_frame>
    <description>Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as:&#xD;
Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm.&#xD;
Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.&#xD;
Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months</time_frame>
    <description>Duration of Response in Patients with Confirmed Response per Investigator</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Erlotinib Mono-Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Rociletinib Mono-Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rociletinib Mono-Therapy</intervention_name>
    <description>Rociletinib will be administered twice daily</description>
    <arm_group_label>Rociletinib Mono-Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erlotinib Mono-Therapy</intervention_name>
    <description>Erlotinib will be administered once a day</description>
    <arm_group_label>Erlotinib Mono-Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed metastatic or unresectable locally&#xD;
             advanced/metastatic NSCLC&#xD;
&#xD;
          2. Documented evidence of a tumor with activating EGFR mutations by local testing.&#xD;
             Patients with exon 20 insertions are not eligible with the exception of patients with&#xD;
             documented evidence of the exon 20 insertion A763_Y764insFQEA in the EGFR gene&#xD;
&#xD;
          3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor&#xD;
             tissue within 60 days of the first day of study treatment, C1D1, and have tissue&#xD;
             available to send to sponsor laboratories or are able to undergo a biopsy during&#xD;
             screening and provide tissue to sponsor laboratories&#xD;
&#xD;
          4. Measureable disease according to RECIST Version 1.1&#xD;
&#xD;
          5. Life expectancy of at least 3 months&#xD;
&#xD;
          6. ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1&#xD;
&#xD;
          7. Minimum age 18 years (in certain territories, the minimum age requirement may be&#xD;
             higher (e.g. 20 years in Japan and Taiwan)&#xD;
&#xD;
          8. Adequate hematological and biological function, confirmed by defined laboratory values&#xD;
&#xD;
          9. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any&#xD;
             study-specific evaluation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Documented evidence of an exon 20 insertion activating mutation other than&#xD;
             A763_Y764insFQEA in the EGFR gene&#xD;
&#xD;
          2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant&#xD;
             chemotherapy is permitted if at least 6 months has elapsed between the end of&#xD;
             chemotherapy and randomization&#xD;
&#xD;
          3. Active second malignancy; i.e., patient known to have potentially fatal cancer present&#xD;
             for which he/she may be (but not necessarily) currently receiving treatment&#xD;
&#xD;
          4. Patients with a history of malignancy that has been completely treated, and currently&#xD;
             with no evidence of that cancer, are permitted to enroll in the trial provided all&#xD;
             chemotherapy was completed &gt; 6 months prior and/or bone marrow transplant &gt; 2 years&#xD;
             prior to first day of study treatment&#xD;
&#xD;
          5. Known pre-existing interstitial lung disease&#xD;
&#xD;
          6. Brain metastases&#xD;
&#xD;
          7. Treatment with prohibited medications less than or equal to 14 days prior to first day&#xD;
             of study treatment&#xD;
&#xD;
          8. Patients who are currently receiving treatment with any medications that have the&#xD;
             potential to prolong the QT interval if that treatment cannot be either discontinued&#xD;
             or switched to a different medication prior to administration of study drug&#xD;
&#xD;
          9. Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib,&#xD;
             AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR&#xD;
&#xD;
         10. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's&#xD;
             method (QTCF) &gt; 450 ms&#xD;
&#xD;
         11. Inability to measure QT interval on ECG&#xD;
&#xD;
         12. Personal or family history of long QT syndrome&#xD;
&#xD;
         13. Implantable pacemaker or implantable cardioverter defibrillator&#xD;
&#xD;
         14. Resting bradycardia &lt; 55 beats/min&#xD;
&#xD;
         15. Non-study related surgical procedures less than or equal to 7 days prior to&#xD;
             administration of study drug. In all cases, the patient must be sufficiently recovered&#xD;
             and stable before treatment administration.&#xD;
&#xD;
         16. Females who are pregnant or breastfeeding&#xD;
&#xD;
         17. Refusal to use adequate contraception for fertile patients (females and males) for 12&#xD;
             weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib&#xD;
&#xD;
         18. Presence of any serious or unstable concomitant systemic disorder incompatible with&#xD;
             the clinical study&#xD;
&#xD;
         19. Any other reason the investigator considers the patient should not participate in the&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Valley Hematology and Oncology Medical Group, Inc.</name>
      <address>
        <city>Burbank</city>
        <state>California</state>
        <zip>91505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Cancer Care Medical Group, Inc.</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Heritage Healthcare</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835-3825</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093-0698</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California, Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90089</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Medical Group</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sansum Clinic</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Medical Oncology Corporation</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <zip>93454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Medical Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oncology Institute of Hope and Innovation</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Specialists of North Florida</name>
      <address>
        <city>Fleming Island</city>
        <state>Florida</state>
        <zip>32003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists and Research Institute</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Medical Specialties</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Hospital Cancer Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Specialists</name>
      <address>
        <city>Niles</city>
        <state>Illinois</state>
        <zip>60714</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harry and Jeanette Weinberg Cancer Institute at Franklin Square</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Walter Reed Army Institute of Research</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology West PC</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Cancer Care Associates, LLC</name>
      <address>
        <city>East Brunswick</city>
        <state>New Jersey</state>
        <zip>08816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Cancer Care Associates</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hollings Cancer Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology, PLLC</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology, PLLC</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC/Norris Comprehensive Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212-3505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology, PA</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Beaumont</name>
      <address>
        <city>Beaumont</city>
        <state>Texas</state>
        <zip>77702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology, P.A.</name>
      <address>
        <city>Bedford</city>
        <state>Texas</state>
        <zip>76022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-8852</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas - MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Plano East</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75075-7753</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists, PC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C.</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yakima Valley Memorial Hospital, North Star Lodge</name>
      <address>
        <city>Yakima</city>
        <state>Washington</state>
        <zip>98902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Fachkliniken München-Gauting</name>
      <address>
        <city>Gauting</city>
        <state>Bayern</state>
        <zip>82131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pius Hospital Oldenburg</name>
      <address>
        <city>Oldenburg</city>
        <state>Niedersachsen</state>
        <zip>26121</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Köln</name>
      <address>
        <city>Köln</city>
        <state>Nordrhein-Westfalen</state>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katholisches Klinikum Mainz, Sankt Hildegardis-Krankenhaus</name>
      <address>
        <city>Mainz</city>
        <state>Rheinland-Pfalz</state>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evangelische Lungenklinik Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <state>New Territories</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile di Livorno</name>
      <address>
        <city>Livorno</city>
        <zip>57124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dong-A University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>602-715</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inha University Hospital</name>
      <address>
        <city>Incheon</city>
        <zip>400-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>463-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Saint Vincent's Hospital</name>
      <address>
        <city>Suwon</city>
        <zip>442-723</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital Linkou</name>
      <address>
        <city>Taoyuan</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <results_first_submitted>January 10, 2019</results_first_submitted>
  <results_first_submitted_qc>April 5, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 30, 2019</results_first_posted>
  <last_update_submitted>April 29, 2019</last_update_submitted>
  <last_update_submitted_qc>April 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cancer</keyword>
  <keyword>metastatic</keyword>
  <keyword>locally advanced</keyword>
  <keyword>lung</keyword>
  <keyword>non-small cell lung cancer</keyword>
  <keyword>NSCLC</keyword>
  <keyword>epidermal growth factor receptor</keyword>
  <keyword>EGFR</keyword>
  <keyword>T790M</keyword>
  <keyword>CO-1686</keyword>
  <keyword>unresectable</keyword>
  <keyword>recurrent</keyword>
  <keyword>EGFR-directed therapy</keyword>
  <keyword>irreversible EGFR inhibitor</keyword>
  <keyword>TIGER</keyword>
  <keyword>rociletinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 22, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT02186301/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>100 subjects recruited from 74 sites, in 7 countries and randomized (1:1) to treatment with rociletinib or erlotinib.Original protocol had rociletinib starting dose of 625mg. In global Amendment 2, starting dose reduced to 500mg. Crossover to rociletinib was permitted however, only 2 patients did so. Safety data for these 2 patients are reported.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Rociletinib 500mg Tablets</title>
          <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="P2">
          <title>Rociletinib 625mg Tablets</title>
          <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="P3">
          <title>Erlotinib 150mg Tablets</title>
          <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="30"/>
                <participants group_id="P3" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0">Patients who are off study for any reason.</participants>
                <participants group_id="P2" count="0">Patients who are off study for any reason.</participants>
                <participants group_id="P3" count="0">Patients who are off study for any reason.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="30"/>
                <participants group_id="P3" count="50"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="27"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Missing</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Rociletinib 500mg Tablets</title>
          <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="B2">
          <title>Rociletinib 625mg Tablets</title>
          <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="B3">
          <title>Erlotinib 150mg Tablets</title>
          <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="50"/>
            <count group_id="B4" value="100"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.0" lower_limit="44" upper_limit="86"/>
                    <measurement group_id="B2" value="67.0" lower_limit="41" upper_limit="85"/>
                    <measurement group_id="B3" value="64" lower_limit="39" upper_limit="88"/>
                    <measurement group_id="B4" value="65" lower_limit="39" upper_limit="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="89"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-White, Non-Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Previous Therapies</title>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.0" lower_limit="0.0" upper_limit="1.0"/>
                    <measurement group_id="B2" value="0.0" lower_limit="0.0" upper_limit="2.0"/>
                    <measurement group_id="B3" value="0.0" lower_limit="0.0" upper_limit="1.0"/>
                    <measurement group_id="B4" value="0.0" lower_limit="0.0" upper_limit="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time Since Diagnosis of NSCLC</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.2" spread="14.12"/>
                    <measurement group_id="B2" value="5.3" spread="10.39"/>
                    <measurement group_id="B3" value="8.2" spread="21.83"/>
                    <measurement group_id="B4" value="7.1" spread="17.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of CNS Metastases</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)</title>
        <description>To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.</description>
        <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months</time_frame>
        <population>Intent-to-treat: All patients randomized.&#xD;
1 patient was not included in analysis, due to discontinuation of study shortly after randomization and prior to first dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Rociletinib 500mg Tablets</title>
            <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Rociletinib 625mg Tablets</title>
            <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O3">
            <title>Erlotinib 150mg Tablets</title>
            <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)</title>
          <description>To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.</description>
          <population>Intent-to-treat: All patients randomized.&#xD;
1 patient was not included in analysis, due to discontinuation of study shortly after randomization and prior to first dose of study drug.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="30"/>
                <count group_id="O3" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="274" lower_limit="109" upper_limit="NA">Upper Confidence Limit is not available because it cannot be calculated.</measurement>
                    <measurement group_id="O2" value="207" lower_limit="112" upper_limit="260"/>
                    <measurement group_id="O3" value="390" lower_limit="282" upper_limit="499"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan-Meier Median</param_type>
            <param_value>274.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>109</ci_lower_limit>
            <ci_upper_limit_na_comment>Upper Confidence Limit is not available because it cannot be calculated</ci_upper_limit_na_comment>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan-Meier Median</param_type>
            <param_value>207.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>112.0</ci_lower_limit>
            <ci_upper_limit>260.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan Meier Median</param_type>
            <param_value>390</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>282.0</ci_lower_limit>
            <ci_upper_limit>499.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Confirmed Response Rate</title>
        <description>Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as:&#xD;
Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm.&#xD;
Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.&#xD;
Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria.</description>
        <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.</time_frame>
        <population>Intent-to-treat: All patients randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Rociletinib 500mg Tablets</title>
            <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Rociletinib 625mg Tablets</title>
            <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O3">
            <title>Erlotinib 150mg Tablets</title>
            <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Confirmed Response Rate</title>
          <description>Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as:&#xD;
Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm.&#xD;
Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.&#xD;
Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria.</description>
          <population>Intent-to-treat: All patients randomized</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="30"/>
                <count group_id="O3" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.0" lower_limit="8.7" upper_limit="49.1"/>
                    <measurement group_id="O2" value="40.0" lower_limit="22.7" upper_limit="59.4"/>
                    <measurement group_id="O3" value="78.0" lower_limit="64.0" upper_limit="88.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percentage</param_type>
            <param_value>25.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>8.7</ci_lower_limit>
            <ci_upper_limit>49.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percentage</param_type>
            <param_value>40.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>22.7</ci_lower_limit>
            <ci_upper_limit>59.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percentage</param_type>
            <param_value>78.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>64.0</ci_lower_limit>
            <ci_upper_limit>88.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Duration of Response in Patients with Confirmed Response per Investigator</description>
        <time_frame>Cycle 1 Day 1 to End of Treatment, up to approximately 35 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rociletinib 500mg Tablets</title>
            <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Rociletinib 625mg Tablets</title>
            <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
          <group group_id="O3">
            <title>Erlotinib 150mg Tablets</title>
            <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Duration of Response in Patients with Confirmed Response per Investigator</description>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="225" lower_limit="113" upper_limit="NA">Upper Confidence Limit is not available because it cannot be calculated.</measurement>
                    <measurement group_id="O2" value="195.5" lower_limit="143.0" upper_limit="617.0"/>
                    <measurement group_id="O3" value="335.0" lower_limit="282.0" upper_limit="480.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan Meier Median</param_type>
            <param_value>225</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>113</ci_lower_limit>
            <ci_upper_limit_na_comment>Upper Confidence Limit is not available because it cannot be calculated.</ci_upper_limit_na_comment>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan Meier Median</param_type>
            <param_value>195.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>143.0</ci_lower_limit>
            <ci_upper_limit>617.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Kaplan Meier Median</param_type>
            <param_value>335.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>282.0</ci_lower_limit>
            <ci_upper_limit>480.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) were reported from the time the first dose of study drug is administered, and until 28 days after the last dose. In addition, study procedure-related AEs that occur after signing of the informed consent form and before first dose of study drug were expected to be reported. Any Serious Adverse Events or Adverse Events of Special Interest were followed until resolution or stabilization, or until patient is lost to follow-up.</time_frame>
      <desc>If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class).&#xD;
Treatment Arm/Groups for subjects (n=2) who crossed over to Rociletinib from Erlotinib are included.</desc>
      <group_list>
        <group group_id="E1">
          <title>Rociletinib 500mg Tablets</title>
          <description>Starting dose of 500mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="E2">
          <title>Rociletinib 625mg Tablets</title>
          <description>Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="E3">
          <title>Erlotinib 150mg Tablets</title>
          <description>Starting dose of 150mg. Taken orally once daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="E4">
          <title>Crossover From Erlotinib 150mg to Rociletinib 500mg</title>
          <description>Patients initially randomized to erlotinib were eligible to participate in an optional crossover phase to receive CO-1686.&#xD;
Starting dose of 500mg CO-1686. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
        <group group_id="E5">
          <title>Crossover From Erlotinib 150mg to Rociletinib 625mg</title>
          <description>Patients initially randomized to erlotinib were eligible to participate in an optional crossover phase to receive CO-1686.&#xD;
Starting dose of 625mg. Taken orally twice daily (continuous 28 day treatment cycle). Treatment duration until radiographically confirmed disease progression.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</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="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Torsade de pointes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute cholangtis, Acute cholecystitis and acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Cardiac murmur</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Polydipsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metastases to bone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Paranasal cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="50" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Combined Terms of QTc Prolongation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Combined Terms of Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Catheter site inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cholecystitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Polydipsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Combined Terms of Rash</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="43" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin fissures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </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>All parties agree to submit all manuscripts or abstracts to all other parties 30 days prior to submission. This will enable all parties to protect proprietary information and to provide comments based on information that may not yet be available to other parties. The sponsor may request a delay in publication if there are important intellectual property concerns relating to publication, but does not have the right to suppress publication of the study results indefinitely.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Vi Nguyen</name_or_title>
      <organization>Clovis Oncology</organization>
      <phone>+1 415 915 9982</phone>
      <email>vnguyen@clovisoncology.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/NCT02186301
org study id: CO-1686-022 (TIGER-1)
nct id: NCT02186301
lead sponsor: 
has dmc: Yes
The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with
      erlotinib in patients whose tumors have specific EGFR mutations and who have not previously
      received any treatment for advanced/metastatic EGFR mutated NSCLC. This study is a
      'Randomized' Study. This means that upon entering the study, patients will be randomly
      assigned to be dosed with either rociletinib twice a day or erlotinib once a day. Patients
      will continue to take either rociletinib or erlotinib until it is no longer beneficial.
This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line
      treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have
      EGFR-activating mutations. The study will consist of Phase 2 and Phase 3 parts which will use
      the same enrollment criteria and treatment assignment principles. Patients will be randomized
      1:1 to erlotinib or rociletinib. The Phase 2 part is an open-label study. In the Phase 3
      part, the sponsor will be blinded to the efficacy and safety results. The study will consist
      of a screening phase to establish study eligibility (including tumor genotype) and document
      baseline measurements, a treatment phase, in which patients will receive either rociletinib
      BID (twice a day) or erlotinib QD (once daily) to ascertain safety and efficacy until
      protocol-defined disease progression, and a follow-up phase, to monitor survival status and
      subsequent NSCLC cancer therapy. In the Phase 2 part only, patients initially randomized to
      erlotinib may be eligible to participate in an optional crossover phase to receive
      rociletinib if they demonstrate the T790M resistance mutation after radiographic progression
      on erlotinib treatment among other eligibility requirements. Patients eligible for this study
      must have EGFR-mutated NSCLC who have not been treated with an EGFR-directed
      therapy.Treatment with rociletinib or erlotinib is continuous. Each 28 day period of
      treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
description: To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.
measure: Confirmed Response Rate
time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
description: Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as:
Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria.
measure: Duration of Response
time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
description: Duration of Response in Patients with Confirmed Response per Investigator
arm group label: Erlotinib Mono-Therapy
arm group type: Active Comparator
arm group label: Rociletinib Mono-Therapy
arm group type: Experimental
intervention type: Drug
intervention name: Rociletinib Mono-Therapy
description: Rociletinib will be administered twice daily
arm group label: Rociletinib Mono-Therapy
intervention type: Drug
intervention name: Erlotinib Mono-Therapy
description: Erlotinib will be administered once a day
arm group label: Erlotinib Mono-Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Hong Kong
country: Italy
country: Korea, Republic of
country: Spain
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Erlotinib Hydrochloride
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 