<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/NCT02987543</url>
  </required_header>
  <id_info>
    <org_study_id>D081DC00007</org_study_id>
    <nct_id>NCT02987543</nct_id>
  </id_info>
  <brief_title>Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)</brief_title>
  <official_title>A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Foundation Medicine, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Myriad Genetics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of olaparib versus&#xD;
      enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate&#xD;
      cancer who have failed prior treatment with a new hormonal agent and have homologous&#xD;
      recombination repair gene mutations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the&#xD;
      efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with&#xD;
      metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with&#xD;
      a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved&#xD;
      in the homologous recombination repair (HRR) pathway. Subjects will be divided into two&#xD;
      cohorts based on HRR gene mutation status.&#xD;
&#xD;
      Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of&#xD;
      enzalutamide or abiraterone acetate) into the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">February 15, 2023</completion_date>
  <primary_completion_date type="Actual">June 4, 2019</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only</measure>
    <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
    <description>The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a &gt;=20% increase in the sum of diameters of target lesions and an absolute increase of &gt;=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as &gt;= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, &gt;=6 weeks later, must show &gt;=2 more new bone lesions (for a total of &gt;=4 new bone lesions since baseline).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only</measure>
    <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
    <description>ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = &gt;=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B</measure>
    <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
    <description>The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Pain Progression - Cohort A Only</measure>
    <time_frame>Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
    <description>Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - Cohort A Only</measure>
    <time_frame>Approximately 35 months after the first patient was randomised.</time_frame>
    <description>Number of Participants with Overall Survival (OS) - Cohort A only.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">387</enrollment>
  <condition>Metastatic Castration-resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Olaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enzalutamide OR abiraterone acetate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Enzalutamide:&#xD;
Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily.&#xD;
Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>olaparib</intervention_name>
    <description>300 mg (2x 150 mg tablets) twice daily</description>
    <arm_group_label>Olaparib</arm_group_label>
    <other_name>Lynparza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>enzalutamide</intervention_name>
    <description>160 mg (4 x 40 mg capsules) once daily</description>
    <arm_group_label>Enzalutamide OR abiraterone acetate</arm_group_label>
    <other_name>XTANDI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>abiraterone acetate</intervention_name>
    <description>1,000 mg (4 x 250 mg tablets) once daily</description>
    <arm_group_label>Enzalutamide OR abiraterone acetate</arm_group_label>
    <other_name>ZYTIGA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>abiraterone acetate</intervention_name>
    <description>1,000 mg (2 x 500 mg tablets) once daily</description>
    <arm_group_label>Enzalutamide OR abiraterone acetate</arm_group_label>
    <other_name>ZYTIGA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>enzalutamide</intervention_name>
    <description>160 mg (4 x 40 mg tablets) once daily</description>
    <arm_group_label>Enzalutamide OR abiraterone acetate</arm_group_label>
    <other_name>XTANDI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Histologically confirmed diagnosis of prostate cancer.&#xD;
&#xD;
          2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).&#xD;
&#xD;
          3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate&#xD;
             and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC .&#xD;
&#xD;
          4. Ongoing therapy with LHRH analog or bilateral orchiectomy.&#xD;
&#xD;
          5. Radiographic progression at study entry while on androgen deprivation therapy (or&#xD;
             after bilateral orchiectomy).&#xD;
&#xD;
          6. Qualifying HRR mutation in tumor tissue.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Any previous treatment with PARP inhibitor, including olaparib.&#xD;
&#xD;
          2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy,&#xD;
             except if for non-prostate cancer indication and last dose &gt; 5 years prior to&#xD;
             randomization.&#xD;
&#xD;
          3. Other malignancy (including MDS and MGUS) within the last 5 years except: adequately&#xD;
             treated non-melanoma skin cancer or other solid tumors curatively treated with no&#xD;
             evidence of disease for ≥5 years.&#xD;
&#xD;
          4. Subjects with known brain metastases.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johann de Bono, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Institute of Cancer Research, United Kingdom</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maha Hussain, M.D., FACP, FASCO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University, United States of America</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jeffersonville</city>
        <state>Indiana</state>
        <zip>47130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10468</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salisbury</city>
        <state>North Carolina</state>
        <zip>28144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Springfield</city>
        <state>Oregon</state>
        <zip>97477</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tualatin</city>
        <state>Oregon</state>
        <zip>97062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29572</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wheeling</city>
        <state>West Virginia</state>
        <zip>26003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1426</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1118AAT</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1120AAT</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caba</city>
        <zip>C1280AEB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>La Rioja</city>
        <zip>5300</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rosario</city>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Adelaide</city>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Box Hill</city>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Clayton</city>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenslopes</city>
        <zip>4120</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Herston</city>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Macquarie University</city>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Melbourne</city>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <city>Nagasaki-shi</city>
        <zip>852-8501</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nagoya-shi</city>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nagoya-shi</city>
        <zip>466-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osaka-shi</city>
        <zip>541-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osaka-shi</city>
        <zip>545-8586</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osakasayama-shi</city>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sagamihara-shi</city>
        <zip>252-0375</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sakura-shi</city>
        <zip>285-8741</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sapporo-shi</city>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shinjuku-ku</city>
        <zip>160-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Suita-shi</city>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sunto-gun</city>
        <zip>411-8777</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yokohama-shi</city>
        <zip>232-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Daegu</city>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Goyang-si</city>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gwangju</city>
        <zip>61469</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06273</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hilversum</city>
        <zip>1213 XZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tilburg</city>
        <zip>5042 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zwolle</city>
        <zip>8025 AB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lørenskog</city>
        <zip>N-1478</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gerona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oviedo</city>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Göteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Solna</city>
        <zip>171 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changhua City</city>
        <zip>50006</zip>
        <country>Taiwan</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>833</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taoyuan City</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Adana</city>
        <zip>01120</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankara</city>
        <zip>06340</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankara</city>
        <zip>06590</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34365</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Karsiyaka</city>
        <zip>35575</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>EC1M 6BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Romford</city>
        <zip>RM7 0BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sutton</city>
        <zip>SM25PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D081DC00007&amp;amp;attachmentIdentifier=fe1712ee-5e58-4f7d-a072-3044f698908d&amp;amp;fileName=D081DC00007_CSP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>CSP redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D081DC00007&amp;amp;attachmentIdentifier=441f6e9d-6f12-410a-9352-dca653de8d9c&amp;amp;fileName=D081DC00007_SAP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>redacted SAP</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <results_first_submitted>June 3, 2020</results_first_submitted>
  <results_first_submitted_qc>September 18, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 12, 2020</results_first_posted>
  <last_update_submitted>March 9, 2023</last_update_submitted>
  <last_update_submitted_qc>March 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic castration-resistant prostate cancer (mCRPC)</keyword>
  <keyword>homologous recombination repair (HRR)</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>Olaparib</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>March 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02987543/Prot_005.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>July 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02987543/SAP_015.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were divided into two cohorts based on HRR gene mutation status. Subjects with mutations in either BRCA1, BRCA2, or ATM are in Cohort A whereas subjects with mutations among 12 other genes involved in the HRR pathway (BARD1, BRIP1, CDK12, CHEK1,CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L) are in Cohort B.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort A Olaparib 300mg bd</title>
          <description>2x150mg film-coated tablets</description>
        </group>
        <group group_id="P2">
          <title>Cohort A Investigators Choice of NHA</title>
          <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
        </group>
        <group group_id="P3">
          <title>Cohort B Olaparib 300mg bd</title>
          <description>2x150mg film-coated tablets</description>
        </group>
        <group group_id="P4">
          <title>Cohort B Investigators Choice of NHA</title>
          <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="162"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="94"/>
                <participants group_id="P4" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="162"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="94"/>
                <participants group_id="P4" count="48"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ongoing study at data cut off</title>
              <participants_list>
                <participants group_id="P1" count="49"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="19"/>
                <participants group_id="P4" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="88"/>
                <participants group_id="P2" count="54"/>
                <participants group_id="P3" count="67"/>
                <participants group_id="P4" count="28"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Screen failure</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </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="7"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort A Olaparib 300mg bd</title>
          <description>2x150mg film-coated tablets</description>
        </group>
        <group group_id="B2">
          <title>Cohort A Investigators Choice of NHA</title>
          <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
        </group>
        <group group_id="B3">
          <title>Cohort B Olaparib 300mg bd</title>
          <description>2x150mg film-coated tablets</description>
        </group>
        <group group_id="B4">
          <title>Cohort B Investigators Choice of NHA</title>
          <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="162"/>
            <count group_id="B2" value="83"/>
            <count group_id="B3" value="94"/>
            <count group_id="B4" value="48"/>
            <count group_id="B5" value="387"/>
          </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="68.0" spread="8.23"/>
                    <measurement group_id="B2" value="68.1" spread="7.36"/>
                    <measurement group_id="B3" value="69.2" spread="8.79"/>
                    <measurement group_id="B4" value="70.3" spread="7.83"/>
                    <measurement group_id="B5" value="68.6" spread="8.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="162"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="94"/>
                    <measurement group_id="B4" value="48"/>
                    <measurement group_id="B5" value="387"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="54"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Secondary</type>
        <title>Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only</title>
        <description>ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = &gt;=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.</description>
        <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
        <population>Evaluable for response</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A Olaparib 300mg bd</title>
            <description>2x150mg film-coated tablets</description>
          </group>
          <group group_id="O2">
            <title>Cohort A Investigators Choice of NHA</title>
            <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
          </group>
        </group_list>
        <measure>
          <title>Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only</title>
          <description>ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = &gt;=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.</description>
          <population>Evaluable for response</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>20.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.18</ci_lower_limit>
            <ci_upper_limit>379.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B</title>
        <description>The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.</description>
        <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A Olaparib 300mg bd</title>
            <description>2x150mg film-coated tablets</description>
          </group>
          <group group_id="O2">
            <title>Cohort A Investigators Choice of NHA</title>
            <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
          </group>
        </group_list>
        <measure>
          <title>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B</title>
          <description>The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.</description>
          <population>Full Analysis Set</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="256"/>
                <count group_id="O2" value="131"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.82" lower_limit="5.52" upper_limit="7.36"/>
                    <measurement group_id="O2" value="3.52" lower_limit="2.2" upper_limit="3.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.49</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.38</ci_lower_limit>
            <ci_upper_limit>0.63</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Pain Progression - Cohort A Only</title>
        <description>Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.</description>
        <time_frame>Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A Olaparib 300mg bd</title>
            <description>2x150mg film-coated tablets</description>
          </group>
          <group group_id="O2">
            <title>Cohort A Investigators Choice of NHA</title>
            <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Pain Progression - Cohort A Only</title>
          <description>Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.</description>
          <population>Full Analysis Set</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="162"/>
                <count group_id="O2" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">NA - Not calculated, estimates cannot be calculated due to too few events.</measurement>
                    <measurement group_id="O2" value="9.92" lower_limit="5.39" upper_limit="NA">NA - Not calculated, estimates cannot be calculated due to too few events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0192</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.22</ci_lower_limit>
            <ci_upper_limit>0.91</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) - Cohort A Only</title>
        <description>Number of Participants with Overall Survival (OS) - Cohort A only.</description>
        <time_frame>Approximately 35 months after the first patient was randomised.</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A Olaparib 300mg bd</title>
            <description>2x150mg film-coated tablets</description>
          </group>
          <group group_id="O2">
            <title>Cohort A Investigators Choice of NHA</title>
            <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) - Cohort A Only</title>
          <description>Number of Participants with Overall Survival (OS) - Cohort A only.</description>
          <population>Full analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Died</title>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Alive at data cut-off</title>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Terminated prior to death (withdrawn consent)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0175</p_value>
            <p_value_desc>2-sided p-value</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.50</ci_lower_limit>
            <ci_upper_limit>0.97</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only</title>
        <description>The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a &gt;=20% increase in the sum of diameters of target lesions and an absolute increase of &gt;=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as &gt;= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, &gt;=6 weeks later, must show &gt;=2 more new bone lesions (for a total of &gt;=4 new bone lesions since baseline).</description>
        <time_frame>Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A Olaparib 300mg bd</title>
            <description>2x150mg film-coated tablets</description>
          </group>
          <group group_id="O2">
            <title>Cohort A Investigators Choice of NHA</title>
            <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
          </group>
        </group_list>
        <measure>
          <title>Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only</title>
          <description>The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a &gt;=20% increase in the sum of diameters of target lesions and an absolute increase of &gt;=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as &gt;= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, &gt;=6 weeks later, must show &gt;=2 more new bone lesions (for a total of &gt;=4 new bone lesions since baseline).</description>
          <population>Full Analysis Set</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="162"/>
                <count group_id="O2" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.39" lower_limit="6.24" upper_limit="9.33"/>
                    <measurement group_id="O2" value="3.55" lower_limit="1.91" upper_limit="3.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.34</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.25</ci_lower_limit>
            <ci_upper_limit>0.47</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of signature of informed consent throughout the treatment period (median duration of treatment of 7.5 and 3.9 months for Olaparib and Investigators Choice of NHA respectively) up to and including the 30-day follow-up period</time_frame>
      <desc>There were 131 subjects randomised to the Investigators Choice of NHA treatment group (Full Analysis Set), however 1 of these subjects did not receive treatment (resulting in 130 in the Safety Analysis Set). Hence, for the Investigators Choice of NHA, the Total number at risk for all-cause mortality = 131 while the Total # at Risk by any Serious Adverse Event = 130 and the Total # at Risk by any Other Adverse Event = 130.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort A+B Olaparib 300mg bd</title>
          <description>2x150mg film-coated tablets</description>
        </group>
        <group group_id="E2">
          <title>Cohort A+B Investigators Choice of NHA</title>
          <description>either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="160" subjects_at_risk="256"/>
                <counts group_id="E2" subjects_affected="88" subjects_at_risk="131"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="94" subjects_at_risk="256"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="23" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cardiopulmonary failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Coronary ostial stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Right ventricular failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Coronary artery stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Diverticulum intestinal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Gastric perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Obstruction gastric</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Obstructive pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Stress ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Duodenal ulcer perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Budd-Chiari syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cellulitis of male external genital organ</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="256"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="256"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Pneumocystis jirovecii pneumoni</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cystitis radiation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Gastroenteritis radiation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Post-traumatic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Spinal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Glioma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Transitional cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ballismus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Calculus bladder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Skin ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Arterial thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="241" subjects_at_risk="256"/>
                <counts group_id="E2" subjects_affected="112" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="154" subjects_affected="110" subjects_at_risk="256"/>
                <counts group_id="E2" events="23" subjects_affected="20" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="256"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="13" subjects_at_risk="256"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="22" subjects_affected="18" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="52" subjects_affected="49" subjects_at_risk="256"/>
                <counts group_id="E2" events="21" subjects_affected="19" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="71" subjects_affected="54" subjects_at_risk="256"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="20" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="136" subjects_affected="109" subjects_at_risk="256"/>
                <counts group_id="E2" events="28" subjects_affected="26" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="82" subjects_affected="49" subjects_at_risk="256"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Stomatitis</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="54" subjects_affected="37" subjects_at_risk="256"/>
                <counts group_id="E2" events="19" subjects_affected="18" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="71" subjects_affected="68" subjects_at_risk="256"/>
                <counts group_id="E2" events="28" subjects_affected="28" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="36" subjects_affected="34" subjects_at_risk="256"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="15" subjects_at_risk="256"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="22" subjects_affected="18" subjects_at_risk="256"/>
                <counts group_id="E2" events="15" subjects_affected="12" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="256"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="88" subjects_affected="78" subjects_at_risk="256"/>
                <counts group_id="E2" events="25" subjects_affected="24" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="26" subjects_affected="25" subjects_at_risk="256"/>
                <counts group_id="E2" events="16" subjects_affected="14" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="44" subjects_affected="36" subjects_at_risk="256"/>
                <counts group_id="E2" events="18" subjects_affected="17" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="256"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="256"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title vocab="MedDRA 22.1">Pain in extremity</sub_title>
                <counts group_id="E1" events="18" subjects_affected="14" subjects_at_risk="256"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="256"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="18" subjects_at_risk="256"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="29" subjects_affected="16" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="256"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="256"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="130"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="32" subjects_affected="29" subjects_at_risk="256"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="130"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="25" subjects_affected="24" subjects_at_risk="256"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="130"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Clinical Lead</name_or_title>
      <organization>AstraZeneca Clinical Study Information Center</organization>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.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/NCT02987543
org study id: D081DC00007
nct id: NCT02987543
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of olaparib versus
      enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate
      cancer who have failed prior treatment with a new hormonal agent and have homologous
      recombination repair gene mutations.
This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the
      efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with
      metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with
      a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved
      in the homologous recombination repair (HRR) pathway. Subjects will be divided into two
      cohorts based on HRR gene mutation status.

      Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of
      enzalutamide or abiraterone acetate) into the trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
description: The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
measure: Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
description: ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.
measure: Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
description: The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
measure: Time to Pain Progression - Cohort A Only
time frame: Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
description: Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
measure: Overall Survival (OS) - Cohort A Only
time frame: Approximately 35 months after the first patient was randomised.
description: Number of Participants with Overall Survival (OS) - Cohort A only.
arm group label: Olaparib
arm group type: Experimental
description: Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions
arm group label: Enzalutamide OR abiraterone acetate
arm group type: Active Comparator
description: Enzalutamide:
Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily.
Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary.
intervention type: Drug
intervention name: olaparib
description: 300 mg (2x 150 mg tablets) twice daily
arm group label: Olaparib
other name: Lynparza
intervention type: Drug
intervention name: enzalutamide
description: 160 mg (4 x 40 mg capsules) once daily
arm group label: Enzalutamide OR abiraterone acetate
other name: XTANDI
intervention type: Drug
intervention name: abiraterone acetate
description: 1,000 mg (4 x 250 mg tablets) once daily
arm group label: Enzalutamide OR abiraterone acetate
other name: ZYTIGA
intervention type: Drug
intervention name: abiraterone acetate
description: 1,000 mg (2 x 500 mg tablets) once daily
arm group label: Enzalutamide OR abiraterone acetate
other name: ZYTIGA
intervention type: Drug
intervention name: enzalutamide
description: 160 mg (4 x 40 mg tablets) once daily
arm group label: Enzalutamide OR abiraterone acetate
other name: XTANDI
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Johann de Bono, M.D., Ph.D.
role: Principal Investigator
affiliation: The Institute of Cancer Research, United Kingdom
last name: Maha Hussain, M.D., FACP, FASCO
role: Principal Investigator
affiliation: Northwestern University, United States of America
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country: Argentina
country: Australia
country: Austria
country: Brazil
country: Canada
country: Denmark
country: France
country: Germany
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: Norway
country: Spain
country: Sweden
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
country: China
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D081DC00007&amp;attachmentIdentifier=fe1712ee-5e58-4f7d-a072-3044f698908d&amp;fileName=D081DC00007_CSP_redacted.pdf&amp;versionIdentifier=
description: CSP redacted
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D081DC00007&amp;attachmentIdentifier=441f6e9d-6f12-410a-9352-dca653de8d9c&amp;fileName=D081DC00007_SAP_redacted.pdf&amp;versionIdentifier=
description: redacted SAP
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Olaparib
mesh term: Abiraterone Acetate
provided document: 
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participant flow: 
baseline: 
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reported events: 
certain agreements: 
point of contact: 