<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/NCT02257736</url>
  </required_header>
  <id_info>
    <org_study_id>CR105505</org_study_id>
    <secondary_id>56021927PCR3001</secondary_id>
    <secondary_id>2014-001718-25</secondary_id>
    <nct_id>NCT02257736</nct_id>
  </id_info>
  <brief_title>An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)</brief_title>
  <official_title>A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aragon Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aragon Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the radiographic progression-free survival (rPFS) of&#xD;
      apalutamide in combination with abiraterone acetate (AA) plus prednisone or prednisolone&#xD;
      (AAP) and AAP in participants with chemotherapy-naive (participants who did not receive any&#xD;
      chemotherapy [treatment of cancer using drugs]) metastatic castration-resistant prostate&#xD;
      cancer (mCRPC) (cancer of prostate gland [gland that makes fluid that aids movement of&#xD;
      sperm]).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (study drug assigned by chance), double-blind (neither the Investigator&#xD;
      nor the participant know the treatment) placebo-controlled and multicenter (when more than 1&#xD;
      hospital or medical school team work on a medical research study) study to determine if&#xD;
      participants with chemotherapy-naive mCRPC will benefit from the addition of apalutamide to&#xD;
      AAP compared with AAP alone. The study consists of 3 phases: Screening phase; Treatment&#xD;
      phase, and Follow-up phase. At the final analysis, the study will be unblinded. After the&#xD;
      Independent Data Monitoring Committee (IDMC) review and the sponsor's subsequent decision&#xD;
      participants will be offered to receive treatment either in the Open-Label Extension Phase or&#xD;
      the Long-Term Extension Phase of study. Participants' safety will be monitored throughout the&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 26, 2014</start_date>
  <completion_date type="Anticipated">October 11, 2023</completion_date>
  <primary_completion_date type="Actual">March 19, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Radiographic Progression-free Survival (rPFS)</measure>
    <time_frame>Up to 3 years and 4 months</time_frame>
    <description>The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (&gt;=) 2 new lesions compared to baseline was observed in less than (&lt;) 12 weeks from randomization and was confirmed by a second bone scan taken &gt;=6 weeks later showing &gt;=2 additional new lesions (a total of &gt;=4 new lesions compared to baseline), b) the first bone scan with &gt;=2 new lesions compared to baseline was observed in &gt;=12 weeks from randomization and the new lesions were verified on the next bone scan &gt;=6 weeks later (a total of &gt;=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 5 years and 10 months</time_frame>
    <description>The OS was defined as the time from randomization to date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Chronic Opioid Use</measure>
    <time_frame>Up to 5 years and 10 months</time_frame>
    <description>Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Initiation of Cytotoxic Chemotherapy</measure>
    <time_frame>Up to 5 years and 10 months</time_frame>
    <description>Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Pain Progression</measure>
    <time_frame>Up to 5 years and 10 months</time_frame>
    <description>Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations &gt;=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where &quot;0&quot; indicates &quot;No pain&quot; and &quot;10&quot; indicates &quot;Pain as bad as you can imagine.&quot; A lower score is better.CRF pain refers to participant's response to global pain assessment &quot;How would you rate your pain over the past 7 days?&quot;with a scale of 0(&quot;No pain&quot;) to 10(&quot;Pain as bad as you can imagine&quot;),that is systematically reported and recorded on the eCRF.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">982</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>Group 1: AAP and apalutamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive apalutamide 240 milligram (mg) (4*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: AAP and Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apalutamide</intervention_name>
    <description>Participants will receive 240 mg (4*60 mg tablets) of apalutamide once daily orally.</description>
    <arm_group_label>Group 1: AAP and apalutamide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abiraterone acetate</intervention_name>
    <description>Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.</description>
    <arm_group_label>Group 1: AAP and apalutamide</arm_group_label>
    <arm_group_label>Group 2: AAP and Placebo</arm_group_label>
    <other_name>ZYTIGA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Participants will receive 5 mg tablet of prednisone twice daily orally.</description>
    <arm_group_label>Group 1: AAP and apalutamide</arm_group_label>
    <arm_group_label>Group 2: AAP and Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive matching placebo to apalutamide once daily orally.</description>
    <arm_group_label>Group 2: AAP and Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adenocarcinoma of the prostate&#xD;
&#xD;
          -  Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic&#xD;
             lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans&#xD;
             (visceral or lymph node disease). If lymph node metastasis is the only evidence of&#xD;
             metastasis, it must be greater than or equal to (&gt;=) 2 centimeter (cm) in the longest&#xD;
             diameter&#xD;
&#xD;
          -  Castration-resistant prostate cancer demonstrated during continuous androgen&#xD;
             deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart with the&#xD;
             last androgen deprivation therapy (PSA) &gt;= 2 nanogram per milliliters (ng/mL)&#xD;
&#xD;
          -  Participants who received a first generation anti-androgen (eg, bicalutamide,&#xD;
             flutamide, nilutamide) must have at least a 6-week washout prior to randomization and&#xD;
             must show continuing disease (PSA) progression (an increase in PSA) after the washout&#xD;
             period&#xD;
&#xD;
          -  Prostate cancer progression documented by prostate-specific antigen (PSA) according to&#xD;
             the Prostate Cancer Clinical Trials Working Group (PCWG2) or radiographic progression&#xD;
             of soft tissue according to modified Response Evaluation Criteria in Solid Tumors,&#xD;
             version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone&#xD;
             according to PCWG2&#xD;
&#xD;
          -  Participants who cross-over from Prednisone alone to open-label apalutamide plus AAP&#xD;
             should still be in the double-blind phase of the study, should be receiving AAP alone&#xD;
             and should have ECOG 0-1-2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Small cell or neuroendocrine carcinoma of the prostate&#xD;
&#xD;
          -  Known brain metastases&#xD;
&#xD;
          -  Prior chemotherapy for prostate cancer, except if administered in the&#xD;
             adjuvant/neoadjuvant setting&#xD;
&#xD;
          -  Previously treated with ketoconazole for prostate cancer for greater than 7 days&#xD;
&#xD;
          -  Therapies that must be discontinued or substituted at least 4 weeks prior to&#xD;
             randomization include the following: a) Medications known to lower the seizure&#xD;
             threshold, b) Herbal and non-herbal products that may decrease PSA levels (example&#xD;
             [eg], saw palmetto, pomegranate) or c) Any investigational agent&#xD;
&#xD;
          -  At Screening need for parenteral or oral opioid analgesics (eg, codeine,&#xD;
             dextropropoxyphene)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>La Mesa</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Modesto</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jensen Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lakeland</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Port Richey</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Melrose</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Niles</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Marrero</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Auburn</city>
        <state>Maine</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tualatin</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lancaster</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Auburn</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wenatchee</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ciudad Automoma Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ciudad de Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cordoba</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>La Rioja</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mendoza</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rosario</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Adelaide</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ashford</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Camperdown</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Herston</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Liverpool</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Malvern</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Melbourne</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Southport</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wahroonga</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Heidelberg</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Woolloongabba</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bruxelles</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gosselies</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Liege</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Namur</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ottignies</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roeselare</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sint-Niklaas</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barretos</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ijui</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Natal</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sao Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Abbotsford</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kelowna</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barrie</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oakville</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Weston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Quebec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Angers Cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Caen Cedex 05</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dijon Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Le Mans Cedex 2</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lyon cedex 03</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris Cedex 15</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Herblain</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toulouse Cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Freiburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Muenster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nuertingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wuppertal</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fukuoka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kanazawa</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kashiwa</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kita-Gun</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kumamoto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kurume</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Matsuyama-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miyazaki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nagasaki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Osaka-Sayama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sakura</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sapporo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ube</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Yokohama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Goyang-Si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seongnam</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chihuahua</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cuernavaca</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Culiacan</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mexico</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oaxaca</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zapopan</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Amsterdam Zuidoost</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Blaricum</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dordrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Heerlen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kursk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Omsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pyatigorsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rostov-on-Don</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Petersburg,</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ufa</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bloemfontein</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Johannesburg</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pretoria</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Alcorcon</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cadiz</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cordoba</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Sebastián de los Reyes</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ayr</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Belfast</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Preston</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Stevenage</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sutton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Westcliff on Sea</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wirral</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>July 21, 2021</results_first_submitted>
  <results_first_submitted_qc>July 21, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 16, 2021</results_first_posted>
  <disposition_first_submitted>March 18, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>March 18, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 26, 2019</disposition_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostatic neoplasms</keyword>
  <keyword>JN56021927</keyword>
  <keyword>ZYTIGA</keyword>
  <keyword>Prednisone</keyword>
  <keyword>Abiraterone acetate</keyword>
  <keyword>Apalutamide</keyword>
  <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>Prednisone</mesh_term>
    <mesh_term>Abiraterone Acetate</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 14, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02257736/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02257736/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Treatment disposition has been reported in participant flow.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
        <group group_id="P2">
          <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="490"/>
                <participants group_id="P2" count="492"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="451"/>
                <participants group_id="P2" count="447"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="365"/>
                <participants group_id="P2" count="327"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance with study drug</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized, not treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
        <group group_id="B2">
          <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
        <group group_id="B3">
          <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="490"/>
            <count group_id="B2" value="492"/>
            <count group_id="B3" value="982"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.7" spread="8.06"/>
                    <measurement group_id="B2" value="71.4" spread="8.34"/>
                    <measurement group_id="B3" value="71.1" spread="8.21"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="490"/>
                    <measurement group_id="B2" value="492"/>
                    <measurement group_id="B3" value="982"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="411"/>
                    <measurement group_id="B2" value="422"/>
                    <measurement group_id="B3" value="833"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="373"/>
                    <measurement group_id="B2" value="365"/>
                    <measurement group_id="B3" value="738"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More than one race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown or Not Reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>ARGENTINA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUSTRALIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BELGIUM</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BRAZIL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CANADA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FRANCE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GERMANY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITALY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>JAPAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MEXICO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NETHERLANDS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RUSSIAN FEDERATION</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SOUTH AFRICA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SOUTH KOREA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPAIN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED KINGDOM</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="128"/>
                    <measurement group_id="B2" value="124"/>
                    <measurement group_id="B3" value="252"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Radiographic Progression-free Survival (rPFS)</title>
        <description>The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (&gt;=) 2 new lesions compared to baseline was observed in less than (&lt;) 12 weeks from randomization and was confirmed by a second bone scan taken &gt;=6 weeks later showing &gt;=2 additional new lesions (a total of &gt;=4 new lesions compared to baseline), b) the first bone scan with &gt;=2 new lesions compared to baseline was observed in &gt;=12 weeks from randomization and the new lesions were verified on the next bone scan &gt;=6 weeks later (a total of &gt;=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.</description>
        <time_frame>Up to 3 years and 4 months</time_frame>
        <population>Intent-to-treat (ITT) population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
          <group group_id="O2">
            <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Progression-free Survival (rPFS)</title>
          <description>The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (&gt;=) 2 new lesions compared to baseline was observed in less than (&lt;) 12 weeks from randomization and was confirmed by a second bone scan taken &gt;=6 weeks later showing &gt;=2 additional new lesions (a total of &gt;=4 new lesions compared to baseline), b) the first bone scan with &gt;=2 new lesions compared to baseline was observed in &gt;=12 weeks from randomization and the new lesions were verified on the next bone scan &gt;=6 weeks later (a total of &gt;=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.</description>
          <population>Intent-to-treat (ITT) population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</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="490"/>
                <count group_id="O2" value="492"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.59" lower_limit="13.86" upper_limit="19.32"/>
                    <measurement group_id="O2" value="23.98" lower_limit="19.71" upper_limit="27.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>The OS was defined as the time from randomization to date of death from any cause.</description>
        <time_frame>Up to 5 years and 10 months</time_frame>
        <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
          <group group_id="O2">
            <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>The OS was defined as the time from randomization to date of death from any cause.</description>
          <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</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="490"/>
                <count group_id="O2" value="492"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.71" lower_limit="31.24" upper_limit="38.28"/>
                    <measurement group_id="O2" value="36.17" lower_limit="32.76" upper_limit="38.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Chronic Opioid Use</title>
        <description>Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.</description>
        <time_frame>Up to 5 years and 10 months</time_frame>
        <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
          <group group_id="O2">
            <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Chronic Opioid Use</title>
          <description>Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.</description>
          <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</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="490"/>
                <count group_id="O2" value="492"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.26" lower_limit="42.02" upper_limit="NA">Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events.</measurement>
                    <measurement group_id="O2" value="46.98" lower_limit="39.23" upper_limit="NA">Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Initiation of Cytotoxic Chemotherapy</title>
        <description>Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.</description>
        <time_frame>Up to 5 years and 10 months</time_frame>
        <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
          <group group_id="O2">
            <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Initiation of Cytotoxic Chemotherapy</title>
          <description>Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.</description>
          <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</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="490"/>
                <count group_id="O2" value="492"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.23" lower_limit="29.54" upper_limit="39.16"/>
                    <measurement group_id="O2" value="36.11" lower_limit="32.23" upper_limit="42.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Pain Progression</title>
        <description>Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations &gt;=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where &quot;0&quot; indicates &quot;No pain&quot; and &quot;10&quot; indicates &quot;Pain as bad as you can imagine.&quot; A lower score is better.CRF pain refers to participant's response to global pain assessment &quot;How would you rate your pain over the past 7 days?&quot;with a scale of 0(&quot;No pain&quot;) to 10(&quot;Pain as bad as you can imagine&quot;),that is systematically reported and recorded on the eCRF.</description>
        <time_frame>Up to 5 years and 10 months</time_frame>
        <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
          <group group_id="O2">
            <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
            <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Pain Progression</title>
          <description>Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations &gt;=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where &quot;0&quot; indicates &quot;No pain&quot; and &quot;10&quot; indicates &quot;Pain as bad as you can imagine.&quot; A lower score is better.CRF pain refers to participant's response to global pain assessment &quot;How would you rate your pain over the past 7 days?&quot;with a scale of 0(&quot;No pain&quot;) to 10(&quot;Pain as bad as you can imagine&quot;),that is systematically reported and recorded on the eCRF.</description>
          <population>ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.</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="490"/>
                <count group_id="O2" value="492"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.51" lower_limit="22.57" upper_limit="29.50"/>
                    <measurement group_id="O2" value="21.82" lower_limit="17.97" upper_limit="25.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 3 years and 4 months</time_frame>
      <desc>Safety Analysis set included all participants who received at least 1 dose of study drug, with treatment assignments designated according to actual study treatment received.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo+ Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
        <group group_id="E2">
          <title>Apalutamide + Abiraterone Acetate - Prednisolone</title>
          <description>Participants received 4*60 mg tablets of apalutamide tablets orally qd with or without food and 4*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 23.0</default_vocab>
        <default_assessment>Non-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="350" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="338" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="166" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="192" subjects_at_risk="490"/>
              </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="5" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Blood Loss Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Disseminated Intravascular Coagulation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Left Ventricular Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Aortic Valve Incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Aortic Valve Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Atrioventricular Block Complete</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cardiac Failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cardiac Failure Chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cardiac Failure Congestive</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Coronary Artery Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Left Ventricular Dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Sinus Node Dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Stress Cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Supraventricular Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Ventricular Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Inappropriate Antidiuretic Hormone Secretion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Visual Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diverticulum Intestinal Haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Duodenal Ulcer Perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Food Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastric Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Inguinal Hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Large Intestine Polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Lumbar Hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Peptic Ulcer Perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Periodontal Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Rectal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Small Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gait Inability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>General Physical Health Deterioration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Generalised Oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Granuloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Multiple Organ Dysfunction Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Systemic Inflammatory Response Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile Duct Stone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cholestasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic Reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Contrast Media Allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Appendicitis Perforated</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Catheter Site Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Clostridium Difficile Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gangrene</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Legionella Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Liver Abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Localised Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Lower Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pneumonia Klebsiella</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pneumonia Legionella</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Post Procedural Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Prostate Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pseudomembranous Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Mycosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Renal Abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Septic Shock</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Staphylococcal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Alcohol Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cervical Vertebral Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Clavicle Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Femoral Neck Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Femur Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Foot Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hand Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hip Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Humerus Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Limb Traumatic Amputation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Lower Limb Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Lumbar Vertebral Fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Multiple Fractures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Muscle Strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pelvic Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Radius Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Rib Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Spinal Compression Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Spinal Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Subdural Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Toxicity to Various Agents</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Traumatic Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Upper Limb Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Blood Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oxygen Saturation Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </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="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diabetes Mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diabetes Mellitus Inadequate Control</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Failure to Thrive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Flank Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pathological Fracture</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Rheumatoid Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Spinal Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Astrocytoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>B-Cell Lymphoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Basal Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bladder Transitional Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cancer Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Colon Cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Colorectal Adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gallbladder Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Gastric Neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hepatic Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Intestinal Metastasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Intraductal Papillary Mucinous Neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Lung Adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Malignant Melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Metastases to Bone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Metastatic Malignant Melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oesophageal Adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oesophageal Neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pancreatic Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Prostate Cancer Metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Small Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Squamous Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Thyroid Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Transitional Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered State of Consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Carotid Artery Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cerebral Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cognitive Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dementia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Embolic Cerebral Infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Haemorrhagic Stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Ischaemic Stroke</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Loss of Consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Nervous System Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Parkinson's Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Peripheral Motor Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Spinal Cord Compression</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Subarachnoid Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Transient Ischaemic Attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device Occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </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="7" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bladder Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Calculus Bladder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oliguria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Renal Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Ureteric Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urethral Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urinary Tract Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Chronic Obstructive Pulmonary Disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pulmonary Oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Rash Pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Skin Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Subcutaneous Emphysema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Coronary Angioplasty</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic Aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Aortic Dissection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Aortic Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Haemodynamic Instability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypertensive Urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pelvic Venous Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Peripheral Arterial Occlusive Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Peripheral Ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 23.0</default_vocab>
        <default_assessment>Non-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="459" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="472" subjects_at_risk="490"/>
              </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="77" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="94" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="96" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="73" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="91" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="76" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="84" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="65" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="134" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="164" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="77" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="52" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="92" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="106" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Rib Fracture</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="53" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Blood Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Blood Pressure Increased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="84" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="136" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Weight Increased</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="490"/>
              </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="60" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="72" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypercholesterolaemia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="73" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="121" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="127" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="133" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="154" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="50" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="61" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="490"/>
              </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="40" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="53" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="490"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot Flush</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="74" subjects_at_risk="490"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="122" subjects_at_risk="489"/>
                <counts group_id="E2" subjects_affected="144" subjects_at_risk="490"/>
              </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>If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study used an electronic handheld device to collect responses for patient-reported outcome (PRO) questionnaires, which might have resulted in a lower-than-expected compliance due to unfamiliarity of the elderly population with the device.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Executive Medical Director</name_or_title>
      <organization>Aragon Pharmaceuticals, Inc.</organization>
      <phone>844-434-4210</phone>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT02257736
org study id: CR105505
secondary id: 56021927PCR3001
secondary id: 2014-001718-25
nct id: NCT02257736
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
The purpose of this study is to compare the radiographic progression-free survival (rPFS) of
      apalutamide in combination with abiraterone acetate (AA) plus prednisone or prednisolone
      (AAP) and AAP in participants with chemotherapy-naive (participants who did not receive any
      chemotherapy [treatment of cancer using drugs]) metastatic castration-resistant prostate
      cancer (mCRPC) (cancer of prostate gland [gland that makes fluid that aids movement of
      sperm]).
This is a randomized (study drug assigned by chance), double-blind (neither the Investigator
      nor the participant know the treatment) placebo-controlled and multicenter (when more than 1
      hospital or medical school team work on a medical research study) study to determine if
      participants with chemotherapy-naive mCRPC will benefit from the addition of apalutamide to
      AAP compared with AAP alone. The study consists of 3 phases: Screening phase; Treatment
      phase, and Follow-up phase. At the final analysis, the study will be unblinded. After the
      Independent Data Monitoring Committee (IDMC) review and the sponsor's subsequent decision
      participants will be offered to receive treatment either in the Open-Label Extension Phase or
      the Long-Term Extension Phase of study. Participants' safety will be monitored throughout the
      study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Radiographic Progression-free Survival (rPFS)
time frame: Up to 3 years and 4 months
description: The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
measure: Overall Survival (OS)
time frame: Up to 5 years and 10 months
description: The OS was defined as the time from randomization to date of death from any cause.
measure: Time to Chronic Opioid Use
time frame: Up to 5 years and 10 months
description: Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
measure: Time to Initiation of Cytotoxic Chemotherapy
time frame: Up to 5 years and 10 months
description: Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
measure: Time to Pain Progression
time frame: Up to 5 years and 10 months
description: Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations >=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.CRF pain refers to participant's response to global pain assessment "How would you rate your pain over the past 7 days?"with a scale of 0("No pain") to 10("Pain as bad as you can imagine"),that is systematically reported and recorded on the eCRF.
arm group label: Group 1: AAP and apalutamide
arm group type: Experimental
description: Participants will receive apalutamide 240 milligram (mg) (4*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).
arm group label: Group 2: AAP and Placebo
arm group type: Placebo Comparator
description: Participants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).
intervention type: Drug
intervention name: Apalutamide
description: Participants will receive 240 mg (4*60 mg tablets) of apalutamide once daily orally.
arm group label: Group 1: AAP and apalutamide
intervention type: Drug
intervention name: Abiraterone acetate
description: Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
arm group label: Group 1: AAP and apalutamide
arm group label: Group 2: AAP and Placebo
other name: ZYTIGA
intervention type: Drug
intervention name: Prednisone
description: Participants will receive 5 mg tablet of prednisone twice daily orally.
arm group label: Group 1: AAP and apalutamide
arm group label: Group 2: AAP and Placebo
intervention type: Drug
intervention name: Placebo
description: Participants will receive matching placebo to apalutamide once daily orally.
arm group label: Group 2: AAP and Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Australia
country: Belgium
country: Brazil
country: Canada
country: France
country: Germany
country: Japan
country: Korea, Republic of
country: Mexico
country: Netherlands
country: Russian Federation
country: South Africa
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Abiraterone Acetate
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study used an electronic handheld device to collect responses for patient-reported outcome (PRO) questionnaires, which might have resulted in a lower-than-expected compliance due to unfamiliarity of the elderly population with the device.
point of contact: 