<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/NCT02253316</url>
  </required_header>
  <id_info>
    <org_study_id>201411060</org_study_id>
    <nct_id>NCT02253316</nct_id>
  </id_info>
  <brief_title>Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma</brief_title>
  <official_title>A Phase II Study of IRD (Ixazomib, Lenalidomide, &amp; Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Multiple Myeloma Research Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to evaluate a treatment regimen called IRD which will&#xD;
      be given to participants after their stem cell transplant in an effort to help prolong the&#xD;
      amount of time the participants are disease-free after transplant. IRD is a three-drug&#xD;
      regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After&#xD;
      4 cycles of IRD, the participants will be randomized to receive maintenance therapy either&#xD;
      with ixazomib or lenalidomide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Based on the further need to improve progression-free survival and overall survival&#xD;
      post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen&#xD;
      of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and&#xD;
      lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate&#xD;
      combination regimens of immunomodulatory drugs and proteasome inhibitors as&#xD;
      consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and&#xD;
      dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral&#xD;
      formulation of ixazomib allows for easier administration when compared to bortezomib.&#xD;
&#xD;
      In this study, following consolidation with IRD, patients will be randomized to maintenance&#xD;
      therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity&#xD;
      and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.&#xD;
&#xD;
      09/23/2019: Upon review of the interim analysis, there will be no further randomizations into&#xD;
      the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm&#xD;
      with the exception of those who discontinue lenalidomide during the consolidation phase due&#xD;
      to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm&#xD;
      following approval from the principal investigator.&#xD;
&#xD;
      09/30/2021: Following analysis 4 in 2021, analysis of the primary endpoint, all patients&#xD;
      receiving lenalidomide maintenance will be transitioned off-study. Patients receiving&#xD;
      ixazomib may remain on trial until disease progression or unacceptable toxicity at the&#xD;
      discretion of the treating physician and the site principal investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 20, 2015</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Actual">February 5, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Improvement in Minimal Residual Disease (MRD)</measure>
    <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
    <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MRD-negative Rate After ASCT</measure>
    <time_frame>Prior to beginning consolidation treatment (Day -28 to Day 0)</time_frame>
    <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity of IRD Consolidation</measure>
    <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
    <description>For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate of IRD Consolidation</measure>
    <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
    <description>For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival of IRD Consolidation</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival of IRD Consolidation</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Toxicity Between the Two Maintenance Arms</measure>
    <time_frame>30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)</time_frame>
    <description>The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Response Rate Between the Two Maintenance Arms</measure>
    <time_frame>Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)</time_frame>
    <description>Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).&#xD;
sCR requires all of the following:&#xD;
CR as defined below&#xD;
Normal free light chain ratio (0.26-1.65)&#xD;
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence&#xD;
CR requires all of the following:&#xD;
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine&#xD;
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)&#xD;
&lt;5% plasma cells in the bone marrow&#xD;
Disappearance of soft tissue plasmacytoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Progression-free Survival Between the Two Maintenance Arms</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Overall Survival Between the Two Maintenance Arms</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms</measure>
    <time_frame>Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of Progression-free Survival With MRD-negativity</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of Progression-free Survival With MRD-positivity</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of Overall Survival With MRD-negativity</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of Overall Survival With MRD-positivity</measure>
    <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
    <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">236</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance Arm 1: Ixazomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance Arm 2: Lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ixazomib</intervention_name>
    <arm_group_label>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</arm_group_label>
    <arm_group_label>Maintenance Arm 1: Ixazomib</arm_group_label>
    <other_name>[14C]-ixazomib</other_name>
    <other_name>[14C]-MLN9708</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <arm_group_label>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</arm_group_label>
    <arm_group_label>Maintenance Arm 2: Lenalidomide</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</arm_group_label>
    <other_name>Aeroseb-Dex</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Decaderm</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Decaspray</other_name>
    <other_name>Deenar</other_name>
    <other_name>Deronil</other_name>
    <other_name>Dex-4</other_name>
    <other_name>Dexace</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dezone</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Maxidex</other_name>
    <other_name>Sk-Dexamethasone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Each patient must meet all of the following inclusion criteria to begin IRD Consolidation:&#xD;
&#xD;
          -  Between the ages of 18 and 70 years of age (inclusive) at time of enrollment&#xD;
&#xD;
          -  Voluntary written consent must be given before performance of any study-related&#xD;
             procedure not part of standard medical care, with the understanding that consent may&#xD;
             be withdrawn by the patient at any time without prejudice to future medical care&#xD;
&#xD;
          -  Confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma&#xD;
             with secondary amyloidosis are eligible.)&#xD;
&#xD;
          -  Received at least two cycles of any regimen as initial systemic therapy for multiple&#xD;
             myeloma and are within 2-16 months of the first dose of initial therapy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance&#xD;
             status 0, 1, or 2&#xD;
&#xD;
          -  Adequate organ function as defined below:&#xD;
&#xD;
        Absolute neutrophil count (ANC) &gt;= 1,000 mm^3 Platelet count &gt;= 75,000/mm^3; platelet&#xD;
        transfusions to help patient meet eligibility criteria are not allowed within 7 days before&#xD;
        study enrollment Total bilirubin &lt;= 1.5 x upper limit of normal range (ULN) Alanine&#xD;
        aminotransferase (ALT) and aspartate aminotransferase (AST) &lt;=3 x ULN Calculated creatinine&#xD;
        clearance &gt;= 30 mL/min&#xD;
&#xD;
          -  Women of childbearing potential must follow pregnancy testing requirements as outlined&#xD;
             in the Revlimid REMS program material. This is defined as either committing to&#xD;
             continued abstinence from heterosexual intercourse or beginning TWO acceptable methods&#xD;
             of contraception (one highly effective method and one additional effective method AT&#xD;
             THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration&#xD;
             of study participation, and for 28 days following the last dose of lenalidomide. Women&#xD;
             of childbearing potential must also agree to ongoing pregnancy testing.&#xD;
&#xD;
          -  Men must agree to use a latex condom during sexual contact with a woman of&#xD;
             childbearing potential even if they have had a successful vasectomy. All patients must&#xD;
             be counseled at a minimum of every 28 days about pregnancy precautions and risks of&#xD;
             fetal exposure. Should a woman become pregnant or suspect she is pregnant while&#xD;
             participating in this study, she must inform her treating physician immediately.&#xD;
&#xD;
          -  All study participants must be registered into the mandatory Revlimind REMS program&#xD;
             and be willing to comply with its requirements. Per standard Revlimid REMS program&#xD;
             requirements, all physicians who prescribe lenalidomide for research subjects enrolled&#xD;
             into this trial, must be registered in, and must comply with, all requirements of the&#xD;
             Revlimid REMS program.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Patients meeting any of the following exclusion criteria are not to be enrolled in the&#xD;
        study:&#xD;
&#xD;
          -  Female patients who are lactating or have a positive serum pregnancy test during the&#xD;
             screening period&#xD;
&#xD;
          -  Evidence of MM disease progression any time prior to enrollment. Progression from&#xD;
             smoldering/asymptomatic MM to symptomatic MM is not exclusionary.&#xD;
&#xD;
          -  Tandem autologous transplantation&#xD;
&#xD;
          -  History of plasma cell leukemia or MM CNS involvement&#xD;
&#xD;
          -  Administration or planned administration of any other concomitant chemotherapy,&#xD;
             immunotherapy, radiotherapy, or any ancillary therapy which would be considered a&#xD;
             treatment of multiple myeloma until Day +28 post-transplant through discontinuation&#xD;
             from study. Patients may be on corticosteroids if they are being given for disorders&#xD;
             other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)&#xD;
&#xD;
          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of treatment according to this protocol.&#xD;
&#xD;
          -  Prior organ transplant requiring immunosuppressive therapy&#xD;
&#xD;
          -  Active hepatitis A, B or C virus infection, or known human immunodeficiency virus&#xD;
             (HIV) positive&#xD;
&#xD;
          -  Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations of any agent&#xD;
&#xD;
          -  Known GI disease or GI procedure that could interfere with the oral absorption or&#xD;
             tolerance of ixazomib&#xD;
&#xD;
          -  Concurrent hematologic or non-hematologic malignancy requiring treatment (other than&#xD;
             multiple myeloma and secondary amyloidosis)&#xD;
&#xD;
          -  Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial&#xD;
             infarction within the previous six months, unstable angina pectoris, clinically&#xD;
             significant repetitive ventricular arrhythmias despite antiarrhythmic treatment,&#xD;
             severe orthostatic hypotension, or clinically important autonomic disease&#xD;
&#xD;
          -  Grade &gt;= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during&#xD;
             the screening period&#xD;
&#xD;
          -  Major surgery within 14 days prior to enrollment&#xD;
&#xD;
          -  Infection requiring systemic antibiotic therapy or other serious infection within 14&#xD;
             days prior to enrollment&#xD;
&#xD;
          -  Participation in other clinical trials, including those with other investigational&#xD;
             agents not included in this trial, within 30 days prior to enrollment and throughout&#xD;
             the duration of this trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ravi Vij, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <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>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University - Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>62864</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</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_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <results_first_submitted>July 29, 2021</results_first_submitted>
  <results_first_submitted_qc>August 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 23, 2021</results_first_posted>
  <disposition_first_submitted>September 24, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>September 24, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 1, 2020</disposition_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Autologous Stem Cell Transplantation</keyword>
  <keyword>Ixazomib</keyword>
  <keyword>Lenalidomide</keyword>
  <keyword>Dexamethasone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Ixazomib</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>April 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT02253316/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
          <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
        </group>
        <group group_id="P2">
          <title>Maintenance Arm 1: Ixazomib</title>
          <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
        </group>
        <group group_id="P3">
          <title>Maintenance Arm 2: Lenalidomide</title>
          <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Consolidation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="236"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="220"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progression</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance</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>Patient Withdrew Logistical Concerns</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Secondary Malignancy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Maintenance</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="99"/>
                <participants group_id="P3" count="116"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="68"/>
                <participants group_id="P3" count="74"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="31"/>
                <participants group_id="P3" count="42"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Patient Withdrew Logistical Concerns</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Secondary Malignancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Still receiving active treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8"/>
                <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>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
          <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="236"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="28" upper_limit="70"/>
                  </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="91"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="145"/>
                  </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="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="217"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="185"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Improvement in Minimal Residual Disease (MRD)</title>
        <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.</description>
        <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
        <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 52 patients in consolidation were not evaluable for the outcome because 26 did not have appropriate VDJ rearrangements on clonoSEQ assessment, 10 did not have sample available from one or both time points, and 16 were removed prior to completion of 4 cycles of IRD.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Improvement in Minimal Residual Disease (MRD)</title>
          <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.</description>
          <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 52 patients in consolidation were not evaluable for the outcome because 26 did not have appropriate VDJ rearrangements on clonoSEQ assessment, 10 did not have sample available from one or both time points, and 16 were removed prior to completion of 4 cycles of IRD.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="184"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MRD-negative Rate After ASCT</title>
        <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing</description>
        <time_frame>Prior to beginning consolidation treatment (Day -28 to Day 0)</time_frame>
        <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 33 patients from consolidation were not evaluable for this outcome because 26 patients did not have appropriate VDJ rearrangements found on clonSEQ assessment and 7 patients did not have a sample available.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>MRD-negative Rate After ASCT</title>
          <description>For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing</description>
          <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 33 patients from consolidation were not evaluable for this outcome because 26 patients did not have appropriate VDJ rearrangements found on clonSEQ assessment and 7 patients did not have a sample available.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="203"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity of IRD Consolidation</title>
        <description>For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.</description>
        <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
        <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 10 patients in consolidation were not evaluable for this outcome because they discontinued prior to 4 cycles of IRD for reasons other than toxicity.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity of IRD Consolidation</title>
          <description>For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.</description>
          <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 10 patients in consolidation were not evaluable for this outcome because they discontinued prior to 4 cycles of IRD for reasons other than toxicity.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="226"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Rate of IRD Consolidation</title>
        <description>For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
        <time_frame>After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)</time_frame>
        <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate of IRD Consolidation</title>
          <description>For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.</description>
          <population>Only participants in the consolidation portion of the trial are evaluable for this outcome measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="236"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival of IRD Consolidation</title>
        <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival of IRD Consolidation</title>
        <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Toxicity Between the Two Maintenance Arms</title>
        <description>The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.</description>
        <time_frame>30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Response Rate Between the Two Maintenance Arms</title>
        <description>Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).&#xD;
sCR requires all of the following:&#xD;
CR as defined below&#xD;
Normal free light chain ratio (0.26-1.65)&#xD;
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence&#xD;
CR requires all of the following:&#xD;
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine&#xD;
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)&#xD;
&lt;5% plasma cells in the bone marrow&#xD;
Disappearance of soft tissue plasmacytoma</description>
        <time_frame>Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)</time_frame>
        <population>This outcome measure is only for participants who went onto the maintenance arms. Participants in the maintenance arms were not evaluable for this outcome measure if they were removed from treatment for reasons other than progressive disease prior to Month 13.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Compare Response Rate Between the Two Maintenance Arms</title>
          <description>Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).&#xD;
sCR requires all of the following:&#xD;
CR as defined below&#xD;
Normal free light chain ratio (0.26-1.65)&#xD;
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence&#xD;
CR requires all of the following:&#xD;
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine&#xD;
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)&#xD;
&lt;5% plasma cells in the bone marrow&#xD;
Disappearance of soft tissue plasmacytoma</description>
          <population>This outcome measure is only for participants who went onto the maintenance arms. Participants in the maintenance arms were not evaluable for this outcome measure if they were removed from treatment for reasons other than progressive disease prior to Month 13.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="109"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="50"/>
                    <measurement group_id="O3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Progression-free Survival Between the Two Maintenance Arms</title>
        <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Overall Survival Between the Two Maintenance Arms</title>
        <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms</title>
        <time_frame>Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)</time_frame>
        <population>This outcome measure is only for participants who went onto the maintenance arms. For the maintenance arms, the overall number of participants analyzed only includes those participants who were MRD positive at the start of maintenance.</population>
        <group_list>
          <group group_id="O1">
            <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
            <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Arm 1: Ixazomib</title>
            <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.&#xD;
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.</description>
          </group>
          <group group_id="O3">
            <title>Maintenance Arm 2: Lenalidomide</title>
            <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms</title>
          <population>This outcome measure is only for participants who went onto the maintenance arms. For the maintenance arms, the overall number of participants analyzed only includes those participants who were MRD positive at the start of maintenance.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="57"/>
                <count group_id="O3" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Association of Progression-free Survival With MRD-negativity</title>
        <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Association of Progression-free Survival With MRD-positivity</title>
        <description>Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Association of Overall Survival With MRD-negativity</title>
        <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Association of Overall Survival With MRD-positivity</title>
        <description>Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.</description>
        <time_frame>Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>-Adverse events were collected from first dose of study treatment through 30 days after the completion of study treatment. -All-cause mortality time frame is from first dose of study treatment through 30 days after the completion of study treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Consolidation: Ixazomib, Lenalidomide, &amp; Dexamethasone</title>
          <description>Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, &amp; dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.</description>
        </group>
        <group group_id="E2">
          <title>Maintenance Arm 1: Ixazomib</title>
          <description>Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.</description>
        </group>
        <group group_id="E3">
          <title>Maintenance Arm 2: Lenalidomide</title>
          <description>Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="44" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="48" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Coronary artery calcification</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Obstruction gastric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Chloecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis - shellfish</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>C. difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Salmonella enteritis infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Ixazomib overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Pancytopenia (myeloma progression)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </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="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute lymphoblastic leukemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Breast cancer in Situ (DCIS)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Compression fracture (myeloma progression)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Myelodysplastic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pancreatic cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Papillary urothelial carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Plasmacytoma (myeloma progression)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Spinal cord compression (myeloma progression)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tubulovillous adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Neuropathic back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Occular migraine (stroke concern)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rigors</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Unintended pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Altered mental status</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Renal calculi</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythroderma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="236" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="99" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="116" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="120" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="59" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hemolysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Thrombotic thrombocytopenic purpura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eustachian tube disfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Middle ear effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Cushingoid</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypoparathyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Thyroiditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic eye irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bulging retinas</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Chalazion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Conjuctivitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eye redness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eye twitching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Ptosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vitreous hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Anal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Changes in teeth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="70" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="35" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="76" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="74" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Esophageal spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Irritable bowel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="67" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="29" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sugar cravings</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Typhlitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Diaphoresis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Diaphoresis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Edema NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Edema trunk</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="108" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="61" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="45" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cirrhosis of the liver</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gallbladder fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gallbladder obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gallbladder pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Liver abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Seasonal allergies</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tongue swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bladder infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>C. difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gum infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Parasitic infection NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Peripheral nerve infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Roseola</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Small intestine infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Testicular infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="56" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Viral infection-NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Yeast infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bit tongue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dog bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Spider bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tick bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Elevated prostate antigen</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fibrinogen decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hemoglobin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="144" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="47" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="59" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="64" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="87" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="97" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="55" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Transminitis NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vitamin B12 deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="104" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="69" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="80" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="35" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </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="9" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Avascular necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="58" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bone spur</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Extensor hallucis longus tear</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Fibromyalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Foot drop</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hernia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Jaw pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Meniscus tear</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Muscle cramps</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Muscle weakness left-sided</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Muscle weakness trunk</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="29" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Osteonecrosis of jaw</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Patellar dislocation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Plantar fascitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Temporomandibular joint syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Twitching in face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Boil</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lump NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Mass NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nevus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nodule</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Plasmacytoma (myeloma progression)</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pulmonary nodule</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Stomach polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Thyroid nodule</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dystonic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Facial nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Left-sided numbness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Movements involuntary</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Parkinsonism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="90" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="65" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Phantom pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tardive dyskinesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dementia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Psychosocial difficulties</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Recurrent dreams</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bladder stones</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Renal calculi</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urostomy obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cystocele</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nipple pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Penile pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Premenstrual syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Prostatic obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vaginal dryness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vaginal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>COPD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="46" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="27" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nasal nares inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sleep apnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Actinic keratosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Allergic contact dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Atopic dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Brittle nails</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Chapped lips</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypohidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Ingrown toenail</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Laceration or abrasion NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nail discoloration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Nail ridging</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Poison ivy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Rosacea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Seborrheic keratosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Shingles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin hypersensitiviy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin lesion NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin peeling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Wart</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Arthroscopy of knee</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Crown repair</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Excision of lipoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hernia repair</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Oral surgery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Orthopedic repair</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Root canal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Spinal surgery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="25" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hyperviscosity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Superficial thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Vascular calcification</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="116"/>
              </event>
              <event>
                <sub_title>Venous stasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="236"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ravi Vij, M.D.</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-454-8323</phone>
      <email>rvij@wustl.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02253316
org study id: 201411060
nct id: NCT02253316
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to evaluate a treatment regimen called IRD which will
      be given to participants after their stem cell transplant in an effort to help prolong the
      amount of time the participants are disease-free after transplant. IRD is a three-drug
      regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After
      4 cycles of IRD, the participants will be randomized to receive maintenance therapy either
      with ixazomib or lenalidomide.
Based on the further need to improve progression-free survival and overall survival
      post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen
      of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and
      lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate
      combination regimens of immunomodulatory drugs and proteasome inhibitors as
      consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and
      dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral
      formulation of ixazomib allows for easier administration when compared to bortezomib.

      In this study, following consolidation with IRD, patients will be randomized to maintenance
      therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity
      and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.

      09/23/2019: Upon review of the interim analysis, there will be no further randomizations into
      the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm
      with the exception of those who discontinue lenalidomide during the consolidation phase due
      to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm
      following approval from the principal investigator.

      09/30/2021: Following analysis 4 in 2021, analysis of the primary endpoint, all patients
      receiving lenalidomide maintenance will be transitioned off-study. Patients receiving
      ixazomib may remain on trial until disease progression or unacceptable toxicity at the
      discretion of the treating physician and the site principal investigator.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Improvement in Minimal Residual Disease (MRD)
time frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
description: For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.
measure: MRD-negative Rate After ASCT
time frame: Prior to beginning consolidation treatment (Day -28 to Day 0)
description: For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing
measure: Toxicity of IRD Consolidation
time frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
description: For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.
measure: Response Rate of IRD Consolidation
time frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
description: For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.
measure: Progression-free Survival of IRD Consolidation
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
measure: Overall Survival of IRD Consolidation
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
measure: Compare Toxicity Between the Two Maintenance Arms
time frame: 30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)
description: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
measure: Compare Response Rate Between the Two Maintenance Arms
time frame: Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)
description: Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).
sCR requires all of the following:
CR as defined below
Normal free light chain ratio (0.26-1.65)
Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
CR requires all of the following:
Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine
If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)
<5% plasma cells in the bone marrow
Disappearance of soft tissue plasmacytoma
measure: Compare Progression-free Survival Between the Two Maintenance Arms
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
measure: Compare Overall Survival Between the Two Maintenance Arms
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
measure: Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms
time frame: Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)
measure: Association of Progression-free Survival With MRD-negativity
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
measure: Association of Progression-free Survival With MRD-positivity
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
measure: Association of Overall Survival With MRD-negativity
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
measure: Association of Overall Survival With MRD-positivity
time frame: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
description: Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
arm group label: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
arm group type: Experimental
description: Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.
arm group label: Maintenance Arm 1: Ixazomib
arm group type: Experimental
description: Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.
arm group label: Maintenance Arm 2: Lenalidomide
arm group type: Experimental
description: Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
intervention type: Biological
intervention name: Ixazomib
arm group label: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
arm group label: Maintenance Arm 1: Ixazomib
other name: [14C]-ixazomib
other name: [14C]-MLN9708
intervention type: Drug
intervention name: Lenalidomide
arm group label: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
arm group label: Maintenance Arm 2: Lenalidomide
other name: Revlimid
intervention type: Drug
intervention name: Dexamethasone
arm group label: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
other name: Aeroseb-Dex
other name: Alba-Dex
other name: Decaderm
other name: Decadrol
other name: Decadron
other name: Decasone R.p.
other name: Decaspray
other name: Deenar
other name: Deronil
other name: Dex-4
other name: Dexace
other name: Dexameth
other name: Dezone
other name: Gammacorten
other name: Hexadrol
other name: Maxidex
other name: Sk-Dexamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ravi Vij, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Lenalidomide
mesh term: Ixazomib
mesh term: BB 1101
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 