<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/NCT03036813</url>
  </required_header>
  <id_info>
    <org_study_id>GBT440-031</org_study_id>
    <secondary_id>C5341043</secondary_id>
    <nct_id>NCT03036813</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)</brief_title>
  <acronym>GBT_HOPE</acronym>
  <official_title>A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</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>
      A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor&#xD;
      Administered Orally to Patients With Sickle Cell Disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, placebo-controlled, double blind, parallel group, multicenter study of&#xD;
      participants, age 12 to 65 years, with SCD. The key purpose for the study is to establish&#xD;
      efficacy and safety of voxelotor as compared with placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">October 8, 2019</completion_date>
  <primary_completion_date type="Actual">October 8, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>This study is a double-blind study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Increase in Hb &gt;1 g/dL From Baseline to Week 24</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Number of participants with increase in Hb &gt;1 g/dL from Baseline to Week 24</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate</measure>
    <time_frame>Baseline to Week 72</time_frame>
    <description>Number of Vaso-Occlusive Crisis (VOC) events averaged per year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Hemolysis Measures</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percentage change from Baseline to week 24 in unconjugated bilirubin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Hemolysis Measures</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Hemolysis Measures</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Hemolysis Measures</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">449</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>voxelotor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>voxelotor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>voxelotor</intervention_name>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_label>Dose 2</arm_group_label>
    <other_name>GBT440</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female study participants with sickle cell disease&#xD;
&#xD;
          2. Participants have had at least 1 episode of vaso-occlusive crisis (VOC) in the past 12&#xD;
             months.&#xD;
&#xD;
          3. Age 12 to 65 years&#xD;
&#xD;
          4. Hemoglobin (Hb) ≥5.5 and ≤10.5 g/dL during screening&#xD;
&#xD;
          5. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at&#xD;
             least 3 months prior to signing the ICF.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. More than 10 VOCs within the past 12 months that required a hospital, emergency room&#xD;
             or clinic visit&#xD;
&#xD;
          2. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also&#xD;
             termed chronic, prophylactic, or preventive transfusion) or have received a RBC&#xD;
             transfusion for any reason within 60 days of signing the ICF&#xD;
&#xD;
          3. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of&#xD;
             signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to&#xD;
             signing the ICF)&#xD;
&#xD;
          4. Hepatic dysfunction characterized by alanine aminotransferase (ALT) &gt;4 × upper limit&#xD;
             of normal&#xD;
&#xD;
          5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit;&#xD;
             calculated by the central laboratory) &lt;30 mL/min/1.73 m^2 or on chronic dialysis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36693</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Alexandria</city>
        <zip>21131</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cairo</city>
        <zip>11566</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zagazig</city>
        <zip>44519</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <zip>75908</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Monza</city>
        <state>Milano</state>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kingston</city>
        <zip>JMAAW15</zip>
        <country>Jamaica</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nairobi</city>
        <zip>42325-00100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nairobi</city>
        <zip>47855</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nairobi</city>
        <zip>59857-00200</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Siaya</city>
        <zip>144-40600</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beirut</city>
        <zip>11072020</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beirut</city>
        <zip>1136044</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tripoli</city>
        <zip>1434</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Den Haag</city>
        <zip>2545 CH</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rotterdam</city>
        <zip>3015 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Muscat</city>
        <zip>123</zip>
        <country>Oman</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Adana</city>
        <zip>01130</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kayseri</city>
        <zip>38039</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mersin</city>
        <zip>33342</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>E11BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>E96SR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>SE17EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>SE59NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>WC1N3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Egypt</country>
    <country>France</country>
    <country>Italy</country>
    <country>Jamaica</country>
    <country>Kenya</country>
    <country>Lebanon</country>
    <country>Netherlands</country>
    <country>Oman</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-031</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <results_first_submitted>October 28, 2020</results_first_submitted>
  <results_first_submitted_qc>January 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 7, 2021</results_first_posted>
  <last_update_submitted>July 17, 2023</last_update_submitted>
  <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>October 27, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03036813/Prot_001.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>October 27, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03036813/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Overall, 449 subjects were screened for this study at 60 study sites. Between January 2017 and May 2018, a total of 274 subjects were randomized at 58 study sites across 12 countries. All 274 randomized subjects were included in the ITT Population. A total of 271 subjects received study drug and were included in the Safety Population.</recruitment_details>
      <pre_assignment_details>Screening procedures were done within 35 days of randomization to assess eligibility.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Voxelotor 900mg</title>
          <description>Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Voxelotor 1500mg</title>
          <description>Participants received voxelotor 1500 mg administered orally, once daily for 72 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Matching placebo; administered orally, once daily for 72 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="63"/>
                <participants group_id="P3" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="27"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliance</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Voxelotor 900mg</title>
          <description>Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Voxelotor 1500mg</title>
          <description>Participants received voxelotor 1500 mg; administered orally, once daily for 72 weeks</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Matching Placebo; administered orally, once daily for 72 weeks</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="92"/>
            <count group_id="B2" value="90"/>
            <count group_id="B3" value="92"/>
            <count group_id="B4" value="274"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>12 to &lt; 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=18 to &lt; 65</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="75"/>
                    <measurement group_id="B4" value="228"/>
                  </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="51"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="159"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="85"/>
                    <measurement group_id="B4" value="253"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>Arab/Middle Eastern</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="63"/>
                    <measurement group_id="B4" value="182"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Multiple</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing/ Not Specified</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>North America</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Egypt</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Kenya</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Jamaica</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oman</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lebanon</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Increase in Hb &gt;1 g/dL From Baseline to Week 24</title>
        <description>Number of participants with increase in Hb &gt;1 g/dL from Baseline to Week 24</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>All randomized subject (ITT population).</population>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Increase in Hb &gt;1 g/dL From Baseline to Week 24</title>
          <description>Number of participants with increase in Hb &gt;1 g/dL from Baseline to Week 24</description>
          <population>All randomized subject (ITT population).</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="92"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="46"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate</title>
        <description>Number of Vaso-Occlusive Crisis (VOC) events averaged per year.</description>
        <time_frame>Baseline to Week 72</time_frame>
        <population>Population excludes 3 subjects (1 in the placebo group and 2 in the voxelotor 1500-mg group) who were not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg; administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500 mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate</title>
          <description>Number of Vaso-Occlusive Crisis (VOC) events averaged per year.</description>
          <population>Population excludes 3 subjects (1 in the placebo group and 2 in the voxelotor 1500-mg group) who were not treated.</population>
          <units>Events per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="1.9" upper_limit="3.1"/>
                    <measurement group_id="O2" value="2.4" lower_limit="1.8" upper_limit="3.1"/>
                    <measurement group_id="O3" value="2.8" lower_limit="2.2" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline in Hemolysis Measures</title>
        <description>Percentage change from Baseline to week 24 in unconjugated bilirubin</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Analysis population includes all randomized patients with a baseline value and at least one post-baseline value</population>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg; administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500 mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Hemolysis Measures</title>
          <description>Percentage change from Baseline to week 24 in unconjugated bilirubin</description>
          <population>Analysis population includes all randomized patients with a baseline value and at least one post-baseline value</population>
          <units>percentage change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="88"/>
                <count group_id="O2" value="85"/>
                <count group_id="O3" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.1" spread="3.41"/>
                    <measurement group_id="O2" value="-29.1" spread="3.46"/>
                    <measurement group_id="O3" value="-2.8" spread="3.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline in Hemolysis Measures</title>
        <description>Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg; administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500 mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants will receive matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Hemolysis Measures</title>
          <description>Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.</description>
          <units>percentage change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="5.13"/>
                    <measurement group_id="O2" value="-6.4" spread="5.17"/>
                    <measurement group_id="O3" value="4.7" spread="5.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline in Hemolysis Measures</title>
        <description>Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).</description>
        <time_frame>Baseline to Week 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg; administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500 mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Hemolysis Measures</title>
          <description>Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).</description>
          <units>Percentage Change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="4.65"/>
                    <measurement group_id="O2" value="-18.0" spread="4.70"/>
                    <measurement group_id="O3" value="6.8" spread="4.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline in Hemolysis Measures</title>
        <description>Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Analysis population includes all randomized patients with a baseline value and at least one post-baseline value</population>
        <group_list>
          <group group_id="O1">
            <title>Voxelotor 900 mg</title>
            <description>Participants received voxelotor 900 mg; administered orally, once daily</description>
          </group>
          <group group_id="O2">
            <title>Voxelotor 1500 mg</title>
            <description>Participants received voxelotor 1500 mg; administered orally, once daily</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants received matching placebo; administered orally, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Hemolysis Measures</title>
          <description>Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)</description>
          <population>Analysis population includes all randomized patients with a baseline value and at least one post-baseline value</population>
          <units>Percentage Change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="90"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="3.68"/>
                    <measurement group_id="O2" value="-4.6" spread="3.69"/>
                    <measurement group_id="O3" value="3.0" spread="3.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>72 Weeks</time_frame>
      <desc>Non-sickle cell disease (Non-SCD) related Adverse Events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Voxelotor 900 mg</title>
          <description>Participants received voxelotor 900 mg, administered orally, once daily</description>
        </group>
        <group group_id="E2">
          <title>Voxelotor 1500 mg</title>
          <description>Participants received voxelotor 1500 mg administered orally, once daily</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Participants received matching placebo; administered orally, once daily</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="2" subjects_at_risk="92"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="92"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="88"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="91"/>
              </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="3" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypersplenism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Reticulocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Haemolytic anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Splenic infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure high output</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blindness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastritis haemorrhagic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Peripherial swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hepatic sequestration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hepatitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Malaria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Brain abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastrointestinal viral infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Sepsis syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Patella fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Medication error</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pain in extemity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Costochondritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Uterine leiomyoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cerebral microhaemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hyperaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash generalised</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Cholecystectomy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </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="85" subjects_at_risk="92"/>
                <counts group_id="E2" subjects_affected="85" subjects_at_risk="88"/>
                <counts group_id="E3" subjects_affected="81" subjects_at_risk="91"/>
              </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="9" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="24" subjects_affected="17" subjects_at_risk="92"/>
                <counts group_id="E2" events="22" subjects_affected="20" subjects_at_risk="88"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="21" subjects_affected="17" subjects_at_risk="92"/>
                <counts group_id="E2" events="21" subjects_affected="16" subjects_at_risk="88"/>
                <counts group_id="E3" events="17" subjects_affected="9" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="92"/>
                <counts group_id="E2" events="17" subjects_affected="13" subjects_at_risk="88"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="20" subjects_affected="13" subjects_at_risk="92"/>
                <counts group_id="E2" events="17" subjects_affected="11" subjects_at_risk="88"/>
                <counts group_id="E3" events="24" subjects_affected="15" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="19" subjects_affected="14" subjects_at_risk="92"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="88"/>
                <counts group_id="E3" events="10" subjects_affected="6" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="92"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="88"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E2" events="8" subjects_affected="3" subjects_at_risk="88"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="27" subjects_affected="15" subjects_at_risk="92"/>
                <counts group_id="E2" events="27" subjects_affected="15" subjects_at_risk="88"/>
                <counts group_id="E3" events="22" subjects_affected="18" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="16" subjects_affected="13" subjects_at_risk="92"/>
                <counts group_id="E2" events="14" subjects_affected="12" subjects_at_risk="88"/>
                <counts group_id="E3" events="15" subjects_affected="12" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="10" subjects_at_risk="92"/>
                <counts group_id="E2" events="13" subjects_affected="11" subjects_at_risk="88"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="92"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="88"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Ocular icterus</sub_title>
                <counts group_id="E1" events="15" subjects_affected="9" subjects_at_risk="92"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="88"/>
                <counts group_id="E3" events="14" subjects_affected="8" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="26" subjects_affected="22" subjects_at_risk="92"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="88"/>
                <counts group_id="E3" events="18" subjects_affected="13" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="88"/>
                <counts group_id="E3" events="15" subjects_affected="13" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Malaria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="92"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E3" events="6" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="92"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="88"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="91"/>
              </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="6" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="92"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="91"/>
              </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="24" subjects_affected="14" subjects_at_risk="92"/>
                <counts group_id="E2" events="33" subjects_affected="18" subjects_at_risk="88"/>
                <counts group_id="E3" events="17" subjects_affected="13" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="25" subjects_affected="12" subjects_at_risk="92"/>
                <counts group_id="E2" events="17" subjects_affected="15" subjects_at_risk="88"/>
                <counts group_id="E3" events="16" subjects_affected="12" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="33" subjects_affected="20" subjects_at_risk="92"/>
                <counts group_id="E2" events="19" subjects_affected="12" subjects_at_risk="88"/>
                <counts group_id="E3" events="22" subjects_affected="19" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="92"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="88"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E3" events="22" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="92"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="22" subjects_affected="20" subjects_at_risk="92"/>
                <counts group_id="E2" events="33" subjects_affected="27" subjects_at_risk="88"/>
                <counts group_id="E3" events="34" subjects_affected="23" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="92"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="91"/>
              </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="7" subjects_affected="6" subjects_at_risk="92"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="88"/>
                <counts group_id="E3" events="11" subjects_affected="10" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="92"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E3" events="6" subjects_affected="4" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="88"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="92"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E3" events="6" subjects_affected="3" subjects_at_risk="91"/>
              </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 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>Margaret Tonda, PharmD, Sr. Director, Clinical Science</name_or_title>
      <organization>Global Blood Therapeutics</organization>
      <phone>(650) 741-7761</phone>
      <email>mtonda@gbt.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/NCT03036813
org study id: GBT440-031
secondary id: C5341043
nct id: NCT03036813
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor
      Administered Orally to Patients With Sickle Cell Disease
This is a randomized, placebo-controlled, double blind, parallel group, multicenter study of
      participants, age 12 to 65 years, with SCD. The key purpose for the study is to establish
      efficacy and safety of voxelotor as compared with placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: This study is a double-blind study.
measure: Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24
time frame: Baseline to Week 24
description: Number of participants with increase in Hb >1 g/dL from Baseline to Week 24
measure: Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate
time frame: Baseline to Week 72
description: Number of Vaso-Occlusive Crisis (VOC) events averaged per year.
measure: Percentage Change From Baseline in Hemolysis Measures
time frame: Baseline to Week 24
description: Percentage change from Baseline to week 24 in unconjugated bilirubin
measure: Percentage Change From Baseline in Hemolysis Measures
time frame: Baseline to Week 24
description: Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.
measure: Percentage Change From Baseline in Hemolysis Measures
time frame: Baseline to Week 24
description: Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).
measure: Percentage Change From Baseline in Hemolysis Measures
time frame: Baseline to Week 24
description: Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)
arm group label: Dose 1
arm group type: Active Comparator
description: voxelotor
arm group label: Dose 2
arm group type: Active Comparator
description: voxelotor
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: voxelotor
arm group label: Dose 1
arm group label: Dose 2
other name: GBT440
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
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country: Canada
country: Egypt
country: France
country: Italy
country: Jamaica
country: Kenya
country: Lebanon
country: Netherlands
country: Oman
country: Turkey
country: United Kingdom
country: United States
url: https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-031
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No
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