<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/NCT02987829</url>
  </required_header>
  <id_info>
    <org_study_id>253PC101</org_study_id>
    <nct_id>NCT02987829</nct_id>
  </id_info>
  <brief_title>Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients</brief_title>
  <official_title>An Open-label Phase 1/2A Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TRC253, an Androgen Receptor Antagonist, in Patients With Metastatic Castration-resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tracon Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Pharmaceutica N.V., Belgium</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Tracon Pharmaceuticals Inc.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, first-in-human, open-label, Phase 1/2A dose-escalation study in which&#xD;
      eligible patients with metastatic castration-resistant prostate carcinoma (mCRPC) will&#xD;
      receive oral doses of TRC253. The study will be conducted in 2 parts: part 1 (dose&#xD;
      escalation) and part 2 (dose expansion).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The patient population consists of men ≥18 years of age with adenocarcinoma of the prostate&#xD;
      with metastatic disease. Patients who have not undergone orchiectomy must have serum&#xD;
      testosterone levels &lt;50 ng/dL determined within 4 weeks prior to start of study drug, and, if&#xD;
      applicable, must have discontinued treatment with first or second generation anti-androgens&#xD;
      as specified in the inclusion criteria.&#xD;
&#xD;
      During Part 1 of the study, patients will be assigned sequentially to increasing TRC253&#xD;
      doses. The starting dose of TRC253 is 40 mg once daily, orally. TRC253 doses will be&#xD;
      escalated in subsequent cohorts after all patients enrolled in a given cohort have completed&#xD;
      the 28-day dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will&#xD;
      follow single-patient dose escalation design until drug-related toxicity occurs. When an&#xD;
      initial drug-related toxicity occurs or DLT in a single patient the cohort will be expanded&#xD;
      according to 3+3 design rules. Subsequent dose levels will enroll patients based on 3+3&#xD;
      design. At the maximum tolerated dose (MTD) or minimum efficacious dose (MED), up to twelve&#xD;
      patients may be enrolled.&#xD;
&#xD;
      Part 2 will consist of two cohorts of initially up to 30 patients (Cohort 1) and up to 30&#xD;
      patients (Cohort 2) to receive TRC253 at the recommended Phase 2 dose (RP2D). The objective&#xD;
      of Part 2 is to gather additional information on the safety, pharmacokinetics (PK) and&#xD;
      pharmacodynamic (PD) characteristics, and the clinical efficacy of TRC253 in a pre-defined&#xD;
      population of patients with metastatic castrate-resistant prostate cancer (mCRPC). Patients&#xD;
      enrolled into Part 2 will have received prior treatment with enzalutamide or apalutamide and&#xD;
      showed characteristics of acquired resistance based on changes in PSA serum levels. Patients&#xD;
      will be centrally screened for the presence of the AR F876L (androgen receptor F876L)&#xD;
      mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR&#xD;
      F876L negative). Cohort 2 may be expanded if a specific molecular mechanism sensitizing the&#xD;
      mCRPC to TRC253 therapy can be identified retrospectively. Additional patients may be&#xD;
      prospectively selected for this specific molecular resistance mechanism and added to Cohort 2&#xD;
      upon recommendation by the medical monitor and Principal Investigators.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 23, 2017</start_date>
  <completion_date type="Actual">November 9, 2020</completion_date>
  <primary_completion_date type="Actual">October 6, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-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 Patients Who Experience Dose Limiting Toxicities by Dose Level</measure>
    <time_frame>5 weeks</time_frame>
    <description>The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria</measure>
    <time_frame>12 weeks</time_frame>
    <description>Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Change in QTcF</measure>
    <time_frame>18 months</time_frame>
    <description>Maximum change in QTcF from baseline by dose level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy</measure>
    <time_frame>4 Weeks</time_frame>
    <description>To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Progression by Dose Level</measure>
    <time_frame>18 months</time_frame>
    <description>Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State</measure>
    <time_frame>28 days</time_frame>
    <description>Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Metastatic Castrate-resistant Prostate Cancer</condition>
  <condition>Adenocarcinoma, Prostate</condition>
  <arm_group>
    <arm_group_label>Dose Level 1: TRC253 40 mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>40 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2: TRC253 80 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>80 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3: TRC253 160 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>160 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 4: TRC253 240 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>240 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 5: TRC253 280 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>280 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 6: TRC253 320 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>320 mg of single-agent TRC253 to be administered as oral capsules once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TRC253</intervention_name>
    <description>TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.</description>
    <arm_group_label>Dose Level 1: TRC253 40 mg daily</arm_group_label>
    <arm_group_label>Dose Level 2: TRC253 80 mg</arm_group_label>
    <arm_group_label>Dose Level 3: TRC253 160 mg</arm_group_label>
    <arm_group_label>Dose Level 4: TRC253 240 mg</arm_group_label>
    <arm_group_label>Dose Level 5: TRC253 280 mg</arm_group_label>
    <arm_group_label>Dose Level 6: TRC253 320 mg</arm_group_label>
    <other_name>AR Antagonist</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must have received at least 2 prior therapies approved for CRPC; including a prior AR&#xD;
             inhibitor (e.g., enzalutamide or apalutamide). (Part 1 only)&#xD;
&#xD;
          2. Must have received enzalutamide or apalutamide. (Note: additional therapies approved&#xD;
             for CRPC prior to enzalutamide or apalutamide are allowed.) (Part 2 only)&#xD;
&#xD;
          3. Must have shown clinical characteristics of acquired resistance to enzalutamide or&#xD;
             apalutamide defined as: decline in serum PSA ≥50% compared to baseline serum levels by&#xD;
             week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease&#xD;
             progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic&#xD;
             criteria. (Part 2 only)&#xD;
&#xD;
             Parts 1 and 2:&#xD;
&#xD;
          4. Histologically confirmed adenocarcinoma of the prostate with metastatic disease.&#xD;
&#xD;
          5. Male ≥18 years of age.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          7. Prior orchiectomy or serum testosterone levels &lt;50 ng/dL determined within 4 weeks&#xD;
             prior to start of study drug.&#xD;
&#xD;
          8. Adequate baseline organ function.&#xD;
&#xD;
          9. Ongoing androgen depletion therapy with a gonadotropin-releasing hormone (GnRH) analog&#xD;
             or inhibitor, or orchiectomy (i.e., surgical or medical castration). Note: patients&#xD;
             who have not undergone orchiectomy must continue GnRH analog therapy for the duration&#xD;
             of this protocol.&#xD;
&#xD;
         10. For patients previously treated with first generation anti-androgens (i.e., flutamide,&#xD;
             nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must&#xD;
             occur &gt;4 weeks (&gt;6 weeks for bicalutamide) prior to start of study drug with no&#xD;
             evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).&#xD;
&#xD;
         11. For patients previously treated with chemotherapy, targeted therapy, immunotherapy, or&#xD;
             treatment with an investigational anticancer agent, discontinuation must have occurred&#xD;
             ≥2 weeks, or after at least 4 half-lives, whichever is longer, prior to study drug&#xD;
             administration. For enzalutamide and apalutamide, the washout period will be at least&#xD;
             3 weeks prior to start of study drug with no evidence of an anti-androgen withdrawal&#xD;
             response (i.e., no decline in serum PSA).&#xD;
&#xD;
         12. For patients previously treated with other agents approved for the treatment of&#xD;
             prostate cancer (5-α reductase inhibitors, estrogens, others), discontinuation of&#xD;
             therapy must have occurred ≥4 weeks prior to start of study drug.&#xD;
&#xD;
         13. Palliative radiotherapy (to bone or soft tissue lesions) must be completed &gt;2 weeks&#xD;
             prior to start of study drug.&#xD;
&#xD;
         14. For patients receiving bone-loss prevention treatment (e.g., bisphosphonates or&#xD;
             denosumab), the patient must be on stable dose ≥4 weeks prior to start of study drug.&#xD;
&#xD;
         15. A man who is sexually active with a woman of childbearing potential must agree to use&#xD;
             a barrier method of birth control during the study and for 4 weeks after receiving the&#xD;
             last dose of study drug. All men must also not donate sperm during the study and for&#xD;
             90 days after receiving the last dose of study drug.&#xD;
&#xD;
         16. Patient must be willing and able to adhere to the prohibitions and restrictions&#xD;
             specified in this protocol.&#xD;
&#xD;
         17. Each patient must sign an informed consent form (ICF) indicating that he understands&#xD;
             the purpose of and procedures required for the study and is willing to participate in&#xD;
             the study. Consent is to be obtained prior to the initiation of any study-related&#xD;
             tests or procedures that are not part of standard-of-care for the patient's disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of seizures.&#xD;
&#xD;
          2. Previously documented or current brain metastases.&#xD;
&#xD;
          3. Untreated spinal cord compression.&#xD;
&#xD;
          4. Positive test result for human immunodeficiency virus.&#xD;
&#xD;
          5. History of clinically significant cardiovascular disease including.&#xD;
&#xD;
          6. Active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface&#xD;
             antigen positivity and/or anti- hepatitis C virus positivity, respectively. Patients&#xD;
             with clinically active or chronic liver disease, including liver cirrhosis of&#xD;
             Child-Pugh class C, are also excluded.&#xD;
&#xD;
          7. Second primary malignancy that has not been in remission for greater than 3 years.&#xD;
             Exceptions that do not require a 3 year remission include: related non-melanoma skin&#xD;
             cancer or resected melanoma in situ.&#xD;
&#xD;
          8. Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse),&#xD;
             dementia or altered mental status or any issue that would impair the ability of the&#xD;
             patient to receive or tolerate the planned treatment, to understand informed consent&#xD;
             or that in the opinion of the investigator would contraindicate the patient's&#xD;
             participation in the study or that would confound the results of the study.&#xD;
&#xD;
          9. Evidence of active viral, bacterial, or systemic fungal infection requiring systemic&#xD;
             treatment within 7 days prior to the first dose of study drug. Patients requiring any&#xD;
             systemic antiviral, antifungal, or antibacterial therapy for active infection must&#xD;
             have completed treatment no less than 7 days prior to the first dose of study drug.&#xD;
&#xD;
         10. Known allergies, hypersensitivity, or intolerance to TRC253 or its excipients.&#xD;
&#xD;
         11. Enrollment in another interventional study.&#xD;
&#xD;
         12. Major surgery (e.g., requiring general anesthesia) within 3 weeks before screening, or&#xD;
             has not fully recovered from prior surgery (i.e., unhealed wound), or surgery planned&#xD;
             during the time the patient is expected to participate in the study. Note: patients&#xD;
             with planned surgical procedures to be conducted under local anesthesia may&#xD;
             participate.&#xD;
&#xD;
         13. Plan to father a child while enrolled in this study or within 90 days after the last&#xD;
             dose of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Freddo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Tracon Pharmaceuticals Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Honor Health</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at Los Angeles</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.</citation>
    <PMID>26903579</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <results_first_submitted>March 1, 2021</results_first_submitted>
  <results_first_submitted_qc>March 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 23, 2021</results_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Androgen Receptor Antagonists</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>May 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT02987829/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>40 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="P2">
          <title>80 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="P3">
          <title>160 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="P4">
          <title>240 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="P5">
          <title>280 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="P6">
          <title>320 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="51"/>
                <participants group_id="P6" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="51"/>
                <participants group_id="P6" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>40 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B2">
          <title>80 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B3">
          <title>160 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B4">
          <title>240 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B5">
          <title>280 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B6">
          <title>320 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="2"/>
            <count group_id="B4" value="7"/>
            <count group_id="B5" value="51"/>
            <count group_id="B6" value="10"/>
            <count group_id="B7" value="72"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="39"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80" lower_limit="80" upper_limit="80"/>
                    <measurement group_id="B2" value="65" lower_limit="65" upper_limit="65"/>
                    <measurement group_id="B3" value="78" lower_limit="75" upper_limit="81"/>
                    <measurement group_id="B4" value="68" lower_limit="56" upper_limit="79"/>
                    <measurement group_id="B5" value="73" lower_limit="56" upper_limit="90"/>
                    <measurement group_id="B6" value="67" lower_limit="58" upper_limit="81"/>
                    <measurement group_id="B7" value="72" lower_limit="56" upper_limit="90"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="51"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/Ethnicity</title>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="42"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other (Patient declined to answer)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="4"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="51"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Who Experience Dose Limiting Toxicities by Dose Level</title>
        <description>The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.</description>
        <time_frame>5 weeks</time_frame>
        <population>All patients who received at least a portion of a dose of TRC253 are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Experience Dose Limiting Toxicities by Dose Level</title>
          <description>The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.</description>
          <population>All patients who received at least a portion of a dose of TRC253 are included in the analysis.</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="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="7"/>
                <count group_id="O5" value="51"/>
                <count group_id="O6" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Determination of the maximum tolerated dose.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <other_analysis_desc>One dose limiting toxicity occurred at 320 mg daily of grade 3 QTc prolongation therefore the 280 mg dose was determined to be the maximum tolerated dose and selected as the phase 2 dose.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria</title>
        <description>Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later</description>
        <time_frame>12 weeks</time_frame>
        <population>Patients with a baseline PSA and at least 1 on study PSA that were confirmed at least 4 weeks later.</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria</title>
          <description>Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later</description>
          <population>Patients with a baseline PSA and at least 1 on study PSA that were confirmed at least 4 weeks later.</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="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="7"/>
                <count group_id="O5" value="51"/>
                <count group_id="O6" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="3"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Change in QTcF</title>
        <description>Maximum change in QTcF from baseline by dose level</description>
        <time_frame>18 months</time_frame>
        <population>Patients who received at least a portion of a dose of TRC253 with a baseline ECG and at least 1 on study ECG.</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Change in QTcF</title>
          <description>Maximum change in QTcF from baseline by dose level</description>
          <population>Patients who received at least a portion of a dose of TRC253 with a baseline ECG and at least 1 on study ECG.</population>
          <units>msec</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="7"/>
                <count group_id="O5" value="50"/>
                <count group_id="O6" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="9" upper_limit="9"/>
                    <measurement group_id="O3" value="22" lower_limit="22" upper_limit="22"/>
                    <measurement group_id="O4" value="44.62" lower_limit="32" upper_limit="64"/>
                    <measurement group_id="O5" value="37.56" lower_limit="0" upper_limit="77"/>
                    <measurement group_id="O6" value="42.63" lower_limit="5" upper_limit="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy</title>
        <description>To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.</description>
        <time_frame>4 Weeks</time_frame>
        <population>TRC253 4 week FDHT-PET response mean SUV based on the 5 hottest lesions (uncorrected)</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy</title>
          <description>To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.</description>
          <population>TRC253 4 week FDHT-PET response mean SUV based on the 5 hottest lesions (uncorrected)</population>
          <units>Percent Change from Baseline</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="1"/>
                <count group_id="O6" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="-34.1" lower_limit="-34.1" upper_limit="-34.1"/>
                    <measurement group_id="O4" value="-2.81" lower_limit="-37.32" upper_limit="31.71"/>
                    <measurement group_id="O5" value="27.78" lower_limit="27.78" upper_limit="27.78"/>
                    <measurement group_id="O6" value="-45.88" lower_limit="-57.32" upper_limit="-34.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Time to Progression by Dose Level</title>
        <description>Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level</description>
        <time_frame>18 months</time_frame>
        <population>In order to be eligible for efficacy analysis patients must have had a baseline CT scan and at least 1 on study CT scan.</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily Dose Levels Combined</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily Dose Levels Combined</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily Dose Levels Combined</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time to Progression by Dose Level</title>
          <description>Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level</description>
          <population>In order to be eligible for efficacy analysis patients must have had a baseline CT scan and at least 1 on study CT scan.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="7"/>
                <count group_id="O5" value="44"/>
                <count group_id="O6" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" lower_limit="NA" upper_limit="NA">The upper and lower confidence level cannot be calculated due to the small sample size</measurement>
                    <measurement group_id="O2" value="9.5" lower_limit="NA" upper_limit="NA">The upper and lower confidence level cannot be calculated due to the small sample size</measurement>
                    <measurement group_id="O3" value="4.8" lower_limit="NA" upper_limit="NA">The upper and lower confidence level cannot be calculated due to the small sample size</measurement>
                    <measurement group_id="O4" value="3.75" lower_limit="2.01" upper_limit="NA">The upper confidence level cannot be calculated due to the small sample size</measurement>
                    <measurement group_id="O5" value="4.64" lower_limit="2.04" upper_limit="7.17"/>
                    <measurement group_id="O6" value="12.20" lower_limit="1.91" upper_limit="NA">The upper confidence level cannot be calculated due to the small sample size</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State</title>
        <description>Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).</description>
        <time_frame>28 days</time_frame>
        <population>Patients who received at least 75% of planned continuous daily dosing after 28 days of daily dosing enrolled in part 1 of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>40 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O2">
            <title>80 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O3">
            <title>160 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O4">
            <title>240 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O5">
            <title>280 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
          <group group_id="O6">
            <title>320 mg TRC253/Daily</title>
            <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State</title>
          <description>Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).</description>
          <population>Patients who received at least 75% of planned continuous daily dosing after 28 days of daily dosing enrolled in part 1 of the study.</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="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="7"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>18 months</time_frame>
      <desc>Duration of participation +28 days</desc>
      <group_list>
        <group group_id="E1">
          <title>40 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="E2">
          <title>80 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="E3">
          <title>160 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="E4">
          <title>240 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="E5">
          <title>280 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
        <group group_id="E6">
          <title>320 mg TRC253/Daily</title>
          <description>Single-agent TRC253 to be administered as oral capsules once daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (14.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oesophageal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Meningeal neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Intramedullary rod insertion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (14.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="48" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Splenic infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye discharge</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eyelid ptosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Corneal neovascularisation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Temperature intolerance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Genital infection fungal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fractured sacrum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Clavicle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hip Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="14" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Joint stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lipoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Extrapyramidal disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypogeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paraparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>VIIth nerve paralysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nocturia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neurogenic Bladder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vesicocutaneous fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Gynaecomastia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Onychomadesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Subclavian artery thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Charles Theuer, MD PhD</name_or_title>
      <organization>Tracon Pharmaceuticals Inc.</organization>
      <phone>8585500780</phone>
      <email>ctheuer@traconpharma.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02987829
org study id: 253PC101
nct id: NCT02987829
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, first-in-human, open-label, Phase 1/2A dose-escalation study in which
      eligible patients with metastatic castration-resistant prostate carcinoma (mCRPC) will
      receive oral doses of TRC253. The study will be conducted in 2 parts: part 1 (dose
      escalation) and part 2 (dose expansion).
The patient population consists of men ≥18 years of age with adenocarcinoma of the prostate
      with metastatic disease. Patients who have not undergone orchiectomy must have serum
      testosterone levels <50 ng/dL determined within 4 weeks prior to start of study drug, and, if
      applicable, must have discontinued treatment with first or second generation anti-androgens
      as specified in the inclusion criteria.

      During Part 1 of the study, patients will be assigned sequentially to increasing TRC253
      doses. The starting dose of TRC253 is 40 mg once daily, orally. TRC253 doses will be
      escalated in subsequent cohorts after all patients enrolled in a given cohort have completed
      the 28-day dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will
      follow single-patient dose escalation design until drug-related toxicity occurs. When an
      initial drug-related toxicity occurs or DLT in a single patient the cohort will be expanded
      according to 3+3 design rules. Subsequent dose levels will enroll patients based on 3+3
      design. At the maximum tolerated dose (MTD) or minimum efficacious dose (MED), up to twelve
      patients may be enrolled.

      Part 2 will consist of two cohorts of initially up to 30 patients (Cohort 1) and up to 30
      patients (Cohort 2) to receive TRC253 at the recommended Phase 2 dose (RP2D). The objective
      of Part 2 is to gather additional information on the safety, pharmacokinetics (PK) and
      pharmacodynamic (PD) characteristics, and the clinical efficacy of TRC253 in a pre-defined
      population of patients with metastatic castrate-resistant prostate cancer (mCRPC). Patients
      enrolled into Part 2 will have received prior treatment with enzalutamide or apalutamide and
      showed characteristics of acquired resistance based on changes in PSA serum levels. Patients
      will be centrally screened for the presence of the AR F876L (androgen receptor F876L)
      mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR
      F876L negative). Cohort 2 may be expanded if a specific molecular mechanism sensitizing the
      mCRPC to TRC253 therapy can be identified retrospectively. Additional patients may be
      prospectively selected for this specific molecular resistance mechanism and added to Cohort 2
      upon recommendation by the medical monitor and Principal Investigators.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients Who Experience Dose Limiting Toxicities by Dose Level
time frame: 5 weeks
description: The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.
measure: Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria
time frame: 12 weeks
description: Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later
measure: Maximum Change in QTcF
time frame: 18 months
description: Maximum change in QTcF from baseline by dose level
measure: Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy
time frame: 4 Weeks
description: To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.
measure: Median Time to Progression by Dose Level
time frame: 18 months
description: Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level
measure: Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State
time frame: 28 days
description: Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).
arm group label: Dose Level 1: TRC253 40 mg daily
arm group type: Experimental
description: 40 mg of single-agent TRC253 to be administered as oral capsules once daily
arm group label: Dose Level 2: TRC253 80 mg
arm group type: Experimental
description: 80 mg of single-agent TRC253 to be administered as oral capsules once daily
arm group label: Dose Level 3: TRC253 160 mg
arm group type: Experimental
description: 160 mg of single-agent TRC253 to be administered as oral capsules once daily
arm group label: Dose Level 4: TRC253 240 mg
arm group type: Experimental
description: 240 mg of single-agent TRC253 to be administered as oral capsules once daily
arm group label: Dose Level 5: TRC253 280 mg
arm group type: Experimental
description: 280 mg of single-agent TRC253 to be administered as oral capsules once daily
arm group label: Dose Level 6: TRC253 320 mg
arm group type: Experimental
description: 320 mg of single-agent TRC253 to be administered as oral capsules once daily
intervention type: Drug
intervention name: TRC253
description: TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
arm group label: Dose Level 1: TRC253 40 mg daily
arm group label: Dose Level 2: TRC253 80 mg
arm group label: Dose Level 3: TRC253 160 mg
arm group label: Dose Level 4: TRC253 240 mg
arm group label: Dose Level 5: TRC253 280 mg
arm group label: Dose Level 6: TRC253 320 mg
other name: AR Antagonist
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: James Freddo, MD
role: Study Director
affiliation: Tracon Pharmaceuticals Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
PMID: 26903579
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Androgen Receptor Antagonists
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 