<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/NCT02214121</url>
  </required_header>
  <id_info>
    <org_study_id>D5136C00007</org_study_id>
    <secondary_id>2014-001006-18</secondary_id>
    <nct_id>NCT02214121</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease</brief_title>
  <acronym>HESTIA 1</acronym>
  <official_title>Multicenter, Open-label, Randomised, Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor Followed by a Double-blind, Randomised, Parallel-group, Placebo-controlled 4 Weeks Extension Phase in Paediatric Patients With Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this Phase II dose-ranging study is to investigate pharmacokinetic (PK) and&#xD;
      pharmacodynamic (PD) properties of various doses of ticagrelor followed by 4 weeks of&#xD;
      twice-daily treatment in paediatric patients with sickle cell disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double&#xD;
      blind, placebo-controlled extension phase in paediatric patients with sickle cell disease&#xD;
      (SCD).&#xD;
&#xD;
      Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of&#xD;
      two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and&#xD;
      pharmacodynamic (PD) measurements will be determined following each dose. Platelet&#xD;
      aggregation will be measured using the VerifyNow™ P2Y12 assay.&#xD;
&#xD;
      Following these 2 single doses, all patients will receive open-label one-week treatment with&#xD;
      ticagrelor twice daily to determine tolerability prior to randomisation into Part B.&#xD;
&#xD;
      Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or&#xD;
      placebo for a 4-week treatment phase.&#xD;
&#xD;
      During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC)&#xD;
      and for other disease manifestations such as daily pain, analgesic use and complications of&#xD;
      SCD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 11, 2014</start_date>
  <completion_date type="Actual">February 27, 2017</completion_date>
  <primary_completion_date type="Actual">February 27, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>P2Y12 Reaction Units (PRU) - Part A</measure>
    <time_frame>PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>P2Y12 Reaction Units (PRU) - Part B</measure>
    <time_frame>PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Part A</measure>
    <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Part B</measure>
    <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve (AUC) - Part A</measure>
    <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
    <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve (AUC) - Part B</measure>
    <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
    <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of Ticagrelor Concentration - Part A</measure>
    <time_frame>In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Ticagrelor Concentration - Part B</measure>
    <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of AR-C124910XX Concentration - Part A</measure>
    <time_frame>In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)</time_frame>
    <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of AR-C124910XX Concentration - Part B</measure>
    <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
    <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Clearance (CL/F) - Part A</measure>
    <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
    <description>The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Clearance (CL/F) - Part B</measure>
    <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
    <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Vaso-occlusive Crises - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days With Pain (Age &gt;=4) - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
    <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Intensity of Pain (Age &gt;=4) - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
    <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days of Analgesic Use (Age &gt;= 4) - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days of Opioid Analgesic Use (Age &gt;=4) - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days of Absence From School or Work (Age &gt;=6) - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Haemorrhagic Events - Part A</measure>
    <time_frame>From randomisation to Part A (week 0) through Visit 4 (week 2)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Haemorrhagic Events - Part B</measure>
    <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Ticagrelor Dose 1a + Dose 2a</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor Dose 1b + Dose 2b</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor Dose 1a + Dose 2a</intervention_name>
    <description>Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.</description>
    <arm_group_label>Ticagrelor Dose 1a + Dose 2a</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor Dose 1b + Dose 2b</intervention_name>
    <description>Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.</description>
    <arm_group_label>Ticagrelor Dose 1b + Dose 2b</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Children aged ≥2 to &lt;18 years of age&#xD;
&#xD;
          -  Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  At risk for haemorrhagic or bradycardic events&#xD;
&#xD;
          -  Significant hepatic impairment&#xD;
&#xD;
          -  Renal failure requiring dialysis&#xD;
&#xD;
          -  Concomitant oral or intravenous therapy with strong CYP3A4 (cytochrome) inhibitors,&#xD;
             CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers.&#xD;
&#xD;
          -  Surgical procedure planned to occur during the study.&#xD;
&#xD;
          -  Patients who are currently pregnant or breastfeeding or planning to become pregnant&#xD;
             during the study.&#xD;
&#xD;
          -  Patients who have known hypersensitivity or contraindication to ticagrelor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kisian</city>
        <zip>100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nairobi</city>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beirut</city>
        <zip>1107 2020</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beirut</city>
        <zip>113-6044</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tripoli</city>
        <zip>1434</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parow</city>
        <zip>7500</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rondebosch</city>
        <zip>7700</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff</city>
        <zip>CF4 4XN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Kenya</country>
    <country>Lebanon</country>
    <country>South Africa</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Egypt</country>
    <country>Ghana</country>
    <country>Italy</country>
    <country>Turkey</country>
  </removed_countries>
  <reference>
    <citation>Hsu LL, Sarnaik S, Williams S, Amilon C, Wissmar J, Berggren A; HESTIA1 Investigators. A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study. Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2.</citation>
    <PMID>30187935</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <results_first_submitted>February 5, 2018</results_first_submitted>
  <results_first_submitted_qc>May 9, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">May 11, 2018</results_first_posted>
  <last_update_submitted>November 22, 2018</last_update_submitted>
  <last_update_submitted_qc>November 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sickle cell anemia</keyword>
  <keyword>paediatric</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <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>March 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT02214121/SAP_000.pdf</document_url>
    </provided_document>
    <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>December 22, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT02214121/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 24 centres, in 6 countries. The first patient was enrolled to Part A of the study on 11 Sep 2014, and the last patient completed Part B of the study on 27 Feb 2017. Recruitment was stopped due to protocol amendment between 8 September 2015 and 1 June 2016.</recruitment_details>
      <pre_assignment_details>46 patients were randomised to Part A of the study (open label). Of the patients completing Part A, 25 were randomised to Part B of the study (double blind)</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A - Ticagrelor</title>
          <description>Randomised treatment group for Part A of the study. Relevant for the Part A period.</description>
        </group>
        <group group_id="P2">
          <title>Part B - Ticagrelor</title>
          <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
        </group>
        <group group_id="P3">
          <title>Part B - Placebo</title>
          <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Patient decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Dev. of study-specific withdrawal crit.</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Patient decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Dev. of study-specific withdrawal crit.</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline characteristics are tabulated by the actual treatment group. This differs from the numbers in the Participant Flow since not all randomised patients received IP and one patient receiving treatment not matching the randomised treatment</population>
      <group_list>
        <group group_id="B1">
          <title>Part A - Ticagrelor</title>
          <description>Actual treatment group for Part A of the study. Relevant for the Part A period.</description>
        </group>
        <group group_id="B2">
          <title>Part B - Ticagrelor</title>
          <description>Actual treatment group for Part B of the study. Relevant for the Part B period.</description>
        </group>
        <group group_id="B3">
          <title>Part B - Placebo</title>
          <description>Actual treatment group for Part B of the study. Relevant for the Part B period.</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="45"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="7"/>
            <count group_id="B4" value="68"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Relevant for the Part A period of the study.</description>
          <population>Including only part A</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.2" spread="3.34"/>
                    <measurement group_id="B4" value="11.2" spread="3.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <description>Relevant for the Part B period of the study.</description>
          <population>Including only part B</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="10.2" spread="3.73"/>
                    <measurement group_id="B3" value="9.7" spread="3.35"/>
                    <measurement group_id="B4" value="10.0" spread="3.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Relevant for the Part A period of the study</description>
          <population>Including only part A</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Relevant for the Part B period of the study.</description>
          <population>Including only part B</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <description>Relevant for the Part A period</description>
          <population>Including only part A</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <description>Relevant for the Part B period of the study.</description>
          <population>Including only part B</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Relevant for the Part A period of the study</description>
          <population>Including only part A</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="45"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Relevant for the Part B period of the study.</description>
          <population>Including only part B</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <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_list>
            </class>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="7"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>P2Y12 Reaction Units (PRU) - Part A</title>
        <time_frame>PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.</time_frame>
        <population>The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor 0.75 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor 0.375 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O4">
            <title>Ticagrelor 0.563 mg/kg</title>
            <description>Single dose received at Visit 3</description>
          </group>
          <group group_id="O5">
            <title>Ticagrelor 1.125 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O6">
            <title>Ticagrelor 2.25 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O7">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O8">
            <title>Ticagrelor 0.563 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O9">
            <title>Ticagrelor 0.75 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units (PRU) - Part A</title>
          <population>The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>P2Y12 reaction units</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="14"/>
                <count group_id="O8" value="9"/>
                <count group_id="O9" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="30"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="17"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="1"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="301.6" spread="46.55"/>
                    <measurement group_id="O2" value="268.0" spread="35.95"/>
                    <measurement group_id="O3" value="295.4" spread="42.30"/>
                    <measurement group_id="O4" value="287.7" spread="34.35"/>
                    <measurement group_id="O5" value="283.7" spread="36.88"/>
                    <measurement group_id="O6" value="277.7" spread="39.36"/>
                    <measurement group_id="O7" value="320" spread="NA">Mean based on one observation.</measurement>
                    <measurement group_id="O8" value="205.4" spread="53.22"/>
                    <measurement group_id="O9" value="214.7" spread="48.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="13"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="278.2" spread="47.20"/>
                    <measurement group_id="O2" value="138.4" spread="70.68"/>
                    <measurement group_id="O3" value="229.0" spread="64.22"/>
                    <measurement group_id="O4" value="176.2" spread="79.53"/>
                    <measurement group_id="O5" value="128.9" spread="37.68"/>
                    <measurement group_id="O6" value="79.9" spread="47.74"/>
                    <measurement group_id="O7" value="271.2" spread="70.35"/>
                    <measurement group_id="O8" value="102.0" spread="72.53"/>
                    <measurement group_id="O9" value="152.0" spread="72.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="28"/>
                    <count group_id="O3" value="2"/>
                    <count group_id="O4" value="14"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="276.0" spread="75.43"/>
                    <measurement group_id="O2" value="189.0" spread="69.84"/>
                    <measurement group_id="O3" value="266.0" spread="57.98"/>
                    <measurement group_id="O4" value="190.4" spread="47.78"/>
                    <measurement group_id="O5" value="191.2" spread="57.59"/>
                    <measurement group_id="O6" value="141.7" spread="69.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="1"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="343.0" spread="38.13"/>
                    <measurement group_id="O3" value="318.3" spread="66.43"/>
                    <measurement group_id="O4" value="318.0" spread="NA">Mean based on one observation.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>P2Y12 Reaction Units (PRU) - Part B</title>
        <time_frame>PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units (PRU) - Part B</title>
          <population>The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
          <units>P2Y12 reaction units</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="282.8" spread="19.26"/>
                    <measurement group_id="O2" value="313.3" spread="20.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="259.6" spread="61.95"/>
                    <measurement group_id="O2" value="217.3" spread="78.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Part A</title>
        <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor 0.75 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor 0.375 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O4">
            <title>Ticagrelor 0.563 mg/kg</title>
            <description>Single dose received at Visit 3</description>
          </group>
          <group group_id="O5">
            <title>Ticagrelor 1.125 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O6">
            <title>Ticagrelor 2.25 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O7">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O8">
            <title>Ticagrelor 0.563 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O9">
            <title>Ticagrelor 0.75 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Part A</title>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="14"/>
                <count group_id="O8" value="9"/>
                <count group_id="O9" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.240" spread="15.2709"/>
                    <measurement group_id="O2" value="162.961" spread="84.9230"/>
                    <measurement group_id="O3" value="52.069" spread="34.4115"/>
                    <measurement group_id="O4" value="96.031" spread="51.4902"/>
                    <measurement group_id="O5" value="269.174" spread="162.2147"/>
                    <measurement group_id="O6" value="566.550" spread="225.9447"/>
                    <measurement group_id="O7" value="13.973" spread="15.3652"/>
                    <measurement group_id="O8" value="111.367" spread="81.1597"/>
                    <measurement group_id="O9" value="157.216" spread="114.8138"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Part B</title>
        <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Part B</title>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.394" spread="13.3671"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve (AUC) - Part A</title>
        <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
        <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor 0.75 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor 0.375 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O4">
            <title>Ticagrelor 0.563 mg/kg</title>
            <description>Single dose received at Visit 3</description>
          </group>
          <group group_id="O5">
            <title>Ticagrelor 1.125 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O6">
            <title>Ticagrelor 2.25 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O7">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O8">
            <title>Ticagrelor 0.563 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O9">
            <title>Ticagrelor 0.75 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve (AUC) - Part A</title>
          <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="14"/>
                <count group_id="O8" value="9"/>
                <count group_id="O9" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="161.9" spread="72.24"/>
                    <measurement group_id="O2" value="1151.9" spread="308.39"/>
                    <measurement group_id="O3" value="437.5" spread="262.24"/>
                    <measurement group_id="O4" value="879.3" spread="236.12"/>
                    <measurement group_id="O5" value="1638.7" spread="521.80"/>
                    <measurement group_id="O6" value="2850.9" spread="1277.39"/>
                    <measurement group_id="O7" value="161.9" spread="72.24"/>
                    <measurement group_id="O8" value="913.5" spread="208.82"/>
                    <measurement group_id="O9" value="1022.4" spread="287.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve (AUC) - Part B</title>
        <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
        <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve (AUC) - Part B</title>
          <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="160.6" spread="88.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Ticagrelor Concentration - Part A</title>
        <time_frame>In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor 0.75 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor 0.375 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O4">
            <title>Ticagrelor 0.563 mg/kg</title>
            <description>Single dose received at Visit 3</description>
          </group>
          <group group_id="O5">
            <title>Ticagrelor 1.125 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O6">
            <title>Ticagrelor 2.25 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O7">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O8">
            <title>Ticagrelor 0.563 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O9">
            <title>Ticagrelor 0.75 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Ticagrelor Concentration - Part A</title>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="14"/>
                <count group_id="O8" value="9"/>
                <count group_id="O9" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="1"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O7" value="2.170" spread="NA">Mean based on one observation.</measurement>
                    <measurement group_id="O8" value="31.937" spread="48.6501"/>
                    <measurement group_id="O9" value="28.066" spread="27.1344"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="8"/>
                    <count group_id="O9" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.713" spread="16.0627"/>
                    <measurement group_id="O2" value="104.243" spread="103.1502"/>
                    <measurement group_id="O3" value="34.069" spread="42.3746"/>
                    <measurement group_id="O4" value="33.294" spread="55.4258"/>
                    <measurement group_id="O5" value="182.558" spread="188.4254"/>
                    <measurement group_id="O6" value="390.568" spread="294.2189"/>
                    <measurement group_id="O8" value="80.414" spread="75.9675"/>
                    <measurement group_id="O9" value="151.520" spread="116.0079"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="14"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.465" spread="8.7427"/>
                    <measurement group_id="O2" value="107.729" spread="62.8343"/>
                    <measurement group_id="O3" value="37.782" spread="31.6890"/>
                    <measurement group_id="O4" value="74.626" spread="50.7053"/>
                    <measurement group_id="O5" value="162.435" spread="161.8489"/>
                    <measurement group_id="O6" value="426.804" spread="212.5385"/>
                    <measurement group_id="O7" value="13.973" spread="15.3652"/>
                    <measurement group_id="O8" value="102.166" spread="78.0785"/>
                    <measurement group_id="O9" value="101.618" spread="65.2415"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.647" spread="4.4533"/>
                    <measurement group_id="O2" value="75.907" spread="31.2786"/>
                    <measurement group_id="O3" value="20.122" spread="9.9383"/>
                    <measurement group_id="O4" value="51.005" spread="24.6435"/>
                    <measurement group_id="O5" value="118.217" spread="42.0873"/>
                    <measurement group_id="O6" value="188.383" spread="111.9267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="16"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.663" spread="3.4061"/>
                    <measurement group_id="O2" value="52.966" spread="29.0297"/>
                    <measurement group_id="O3" value="19.435" spread="15.7259"/>
                    <measurement group_id="O4" value="45.502" spread="17.8950"/>
                    <measurement group_id="O5" value="69.708" spread="44.3168"/>
                    <measurement group_id="O6" value="125.279" spread="89.0005"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.880" spread="3.3171"/>
                    <measurement group_id="O3" value="15.699" spread="20.7596"/>
                    <measurement group_id="O4" value="15.691" spread="15.1392"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Ticagrelor Concentration - Part B</title>
        <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of Ticagrelor Concentration - Part B</title>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.478" spread="3.9580"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.677" spread="9.4275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.144" spread="12.4711"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.605" spread="14.4979"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of AR-C124910XX Concentration - Part A</title>
        <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
        <time_frame>In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor 0.75 mg/kg</title>
            <description>Single dose received at Visit 2.</description>
          </group>
          <group group_id="O3">
            <title>Ticagrelor 0.375 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O4">
            <title>Ticagrelor 0.563 mg/kg</title>
            <description>Single dose received at Visit 3</description>
          </group>
          <group group_id="O5">
            <title>Ticagrelor 1.125 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O6">
            <title>Ticagrelor 2.25 mg/kg</title>
            <description>Single dose received at Visit 3.</description>
          </group>
          <group group_id="O7">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O8">
            <title>Ticagrelor 0.563 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
          <group group_id="O9">
            <title>Ticagrelor 0.75 mg/kg Bid</title>
            <description>Repeated bid treatment between Visit 3 and Visit 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of AR-C124910XX Concentration - Part A</title>
          <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="14"/>
                <count group_id="O8" value="9"/>
                <count group_id="O9" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="1"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O7" value="1.250" spread="NA">Mean based on one observation.</measurement>
                    <measurement group_id="O8" value="17.380" spread="10.0399"/>
                    <measurement group_id="O9" value="20.359" spread="15.0788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="8"/>
                    <count group_id="O9" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.782" spread="1.6604"/>
                    <measurement group_id="O2" value="16.302" spread="22.4614"/>
                    <measurement group_id="O3" value="4.577" spread="7.8610"/>
                    <measurement group_id="O4" value="3.708" spread="13.3332"/>
                    <measurement group_id="O5" value="30.070" spread="44.2950"/>
                    <measurement group_id="O6" value="63.088" spread="84.2091"/>
                    <measurement group_id="O8" value="24.945" spread="15.6547"/>
                    <measurement group_id="O9" value="43.986" spread="29.8127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="7"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="14"/>
                    <count group_id="O8" value="9"/>
                    <count group_id="O9" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.681" spread="2.0733"/>
                    <measurement group_id="O2" value="33.256" spread="25.3854"/>
                    <measurement group_id="O3" value="11.757" spread="13.3322"/>
                    <measurement group_id="O4" value="15.918" spread="17.4849"/>
                    <measurement group_id="O5" value="52.932" spread="69.1056"/>
                    <measurement group_id="O6" value="149.772" spread="71.3624"/>
                    <measurement group_id="O7" value="4.026" spread="4.7624"/>
                    <measurement group_id="O8" value="37.013" spread="32.7650"/>
                    <measurement group_id="O9" value="44.690" spread="31.6577"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="18"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.071" spread="1.2770"/>
                    <measurement group_id="O2" value="29.860" spread="13.8726"/>
                    <measurement group_id="O3" value="7.630" spread="6.3730"/>
                    <measurement group_id="O4" value="17.015" spread="7.9272"/>
                    <measurement group_id="O5" value="50.887" spread="25.6964"/>
                    <measurement group_id="O6" value="101.370" spread="44.6207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="16"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="9"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.646" spread="1.0427"/>
                    <measurement group_id="O2" value="25.276" spread="10.8318"/>
                    <measurement group_id="O3" value="9.762" spread="2.3304"/>
                    <measurement group_id="O4" value="16.703" spread="5.8115"/>
                    <measurement group_id="O5" value="35.716" spread="22.3351"/>
                    <measurement group_id="O6" value="76.941" spread="39.9167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.715" spread="1.0226"/>
                    <measurement group_id="O3" value="6.176" spread="6.3168"/>
                    <measurement group_id="O4" value="9.232" spread="2.5385"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of AR-C124910XX Concentration - Part B</title>
        <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
        <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>Assessment of AR-C124910XX Concentration - Part B</title>
          <description>AR-C124910XX is the active metabolite of Ticagrelor</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.810" spread="1.1213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.865" spread="1.6443"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.160" spread="3.1503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.953" spread="4.1179"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Clearance (CL/F) - Part A</title>
        <description>The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
        <time_frame>PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Overall</title>
            <description>All patients receiving Ticagrelor during Part A.</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Clearance (CL/F) - Part A</title>
          <description>The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.50" spread="7.531"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Clearance (CL/F) - Part B</title>
        <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
        <time_frame>PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.</time_frame>
        <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor 0.125 mg/kg Bid</title>
            <description>Repeated bid treatment during Part B.</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Clearance (CL/F) - Part B</title>
          <description>The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.</description>
          <population>The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.15" spread="6.673"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Vaso-occlusive Crises - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Vaso-occlusive Crises - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Number of events</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="2.00"/>
                    <measurement group_id="O2" value="0.6" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Number of events</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.41"/>
                    <measurement group_id="O2" value="0.1" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.52" spread="11.816"/>
                    <measurement group_id="O2" value="1.34" spread="3.788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days With Pain (Age &gt;=4) - Part B</title>
        <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days With Pain (Age &gt;=4) - Part B</title>
          <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.01" spread="34.065"/>
                    <measurement group_id="O2" value="31.78" spread="23.731"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Intensity of Pain (Age &gt;=4) - Part B</title>
        <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Intensity of Pain (Age &gt;=4) - Part B</title>
          <description>Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain</description>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Mean score on scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall - Part B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.40" spread="2.027"/>
                    <measurement group_id="O2" value="0.87" spread="0.493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1st week</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.64" spread="2.603"/>
                    <measurement group_id="O2" value="1.36" spread="0.827"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2nd week</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.11" spread="2.236"/>
                    <measurement group_id="O2" value="0.38" spread="0.525"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3rd week</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.06" spread="1.881"/>
                    <measurement group_id="O2" value="0.67" spread="1.116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4th week</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.46" spread="2.624"/>
                    <measurement group_id="O2" value="0.83" spread="0.901"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days of Analgesic Use (Age &gt;= 4) - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days of Analgesic Use (Age &gt;= 4) - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.79" spread="20.838"/>
                    <measurement group_id="O2" value="18.56" spread="19.110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days of Opioid Analgesic Use (Age &gt;=4) - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days of Opioid Analgesic Use (Age &gt;=4) - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.46" spread="22.502"/>
                    <measurement group_id="O2" value="0.54" spread="1.537"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days of Absence From School or Work (Age &gt;=6) - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days of Absence From School or Work (Age &gt;=6) - Part B</title>
          <population>All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.</population>
          <units>Percentage of days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.87" spread="10.865"/>
                    <measurement group_id="O2" value="5.95" spread="9.494"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Haemorrhagic Events - Part A</title>
        <time_frame>From randomisation to Part A (week 0) through Visit 4 (week 2)</time_frame>
        <population>All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A - Ticagrelor</title>
            <description>Randomised treatment group for Part A of the study. Relevant for the Part A period.</description>
          </group>
        </group_list>
        <measure>
          <title>Haemorrhagic Events - Part A</title>
          <population>All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.</population>
          <units>Number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Haemorrhagic Events - Part B</title>
        <time_frame>During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).</time_frame>
        <population>All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received. Erroneously treated patients will be accounted for in the actual treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B - Ticagrelor</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
          <group group_id="O2">
            <title>Part B - Placebo</title>
            <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
          </group>
        </group_list>
        <measure>
          <title>Haemorrhagic Events - Part B</title>
          <population>All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received. Erroneously treated patients will be accounted for in the actual treatment group.</population>
          <units>Number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>SAEs were collected from Visit 1 and AEs from Visit 2. SAEs and Other AEs are presented by study period, where Part A consists of the time from randomization to Part A through Visit 4. Part B starts the day after Visit 4 and continues until Visit 8.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Part A - Ticagrelor</title>
          <description>Randomised treatment group for Part A of the study. Relevant for the Part A period.</description>
        </group>
        <group group_id="E2">
          <title>Part B - Ticagrelor</title>
          <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
        </group>
        <group group_id="E3">
          <title>Part B - Placebo</title>
          <description>Randomised treatment group for Part B of the study. Relevant for the Part B period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 19.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Sickle cell anemia with crisis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute chest syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 19.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Sickle cell anemia with crisis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tympanic membrane perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tinea infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </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="7" subjects_affected="5" subjects_at_risk="45"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="45"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </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="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </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>No publication can be made in advance of the first multicenter publication by the sponsor. Any publication will be submitted to the sponsor for review prior to the being published. The sponsor has the right to defer this publication for a period between 60 days to 6 months. The sponsor has the right to restrict the use of confidential information in any of the publications submitted.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Brilinta Global Clinical Lead</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>+46 31 776 1000</phone>
      <email>kontakt@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02214121
org study id: D5136C00007
secondary id: 2014-001006-18
nct id: NCT02214121
lead sponsor: 
has dmc: No
The purpose of this Phase II dose-ranging study is to investigate pharmacokinetic (PK) and
      pharmacodynamic (PD) properties of various doses of ticagrelor followed by 4 weeks of
      twice-daily treatment in paediatric patients with sickle cell disease
This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double
      blind, placebo-controlled extension phase in paediatric patients with sickle cell disease
      (SCD).

      Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of
      two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and
      pharmacodynamic (PD) measurements will be determined following each dose. Platelet
      aggregation will be measured using the VerifyNow™ P2Y12 assay.

      Following these 2 single doses, all patients will receive open-label one-week treatment with
      ticagrelor twice daily to determine tolerability prior to randomisation into Part B.

      Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or
      placebo for a 4-week treatment phase.

      During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC)
      and for other disease manifestations such as daily pain, analgesic use and complications of
      SCD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: P2Y12 Reaction Units (PRU) - Part A
time frame: PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.
measure: P2Y12 Reaction Units (PRU) - Part B
time frame: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
measure: Maximum Plasma Concentration (Cmax) - Part A
time frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
measure: Maximum Plasma Concentration (Cmax) - Part B
time frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
measure: Area Under the Plasma Concentration Time Curve (AUC) - Part A
time frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
description: The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
measure: Area Under the Plasma Concentration Time Curve (AUC) - Part B
time frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
description: The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
measure: Assessment of Ticagrelor Concentration - Part A
time frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
measure: Assessment of Ticagrelor Concentration - Part B
time frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
measure: Assessment of AR-C124910XX Concentration - Part A
time frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
description: AR-C124910XX is the active metabolite of Ticagrelor
measure: Assessment of AR-C124910XX Concentration - Part B
time frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
description: AR-C124910XX is the active metabolite of Ticagrelor
measure: Oral Clearance (CL/F) - Part A
time frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
description: The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.
measure: Oral Clearance (CL/F) - Part B
time frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
description: The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
measure: Number of Vaso-occlusive Crises - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Percentage of Days With Pain (Age >=4) - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
description: Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
measure: Mean Intensity of Pain (Age >=4) - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
description: Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
measure: Percentage of Days of Analgesic Use (Age >= 4) - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Percentage of Days of Absence From School or Work (Age >=6) - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
measure: Haemorrhagic Events - Part A
time frame: From randomisation to Part A (week 0) through Visit 4 (week 2)
measure: Haemorrhagic Events - Part B
time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
arm group label: Ticagrelor Dose 1a + Dose 2a
arm group type: Other
description: Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.
arm group label: Ticagrelor Dose 1b + Dose 2b
arm group type: Other
description: Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.
intervention type: Drug
intervention name: Ticagrelor Dose 1a + Dose 2a
description: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
arm group label: Ticagrelor Dose 1a + Dose 2a
intervention type: Drug
intervention name: Ticagrelor Dose 1b + Dose 2b
description: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
arm group label: Ticagrelor Dose 1b + Dose 2b
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gender: All
minimum age: 2 Years
maximum age: 17 Years
healthy volunteers: No
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country: Canada
country: Kenya
country: Lebanon
country: South Africa
country: United Kingdom
country: United States
country: Egypt
country: Ghana
country: Italy
country: Turkey
citation: Hsu LL, Sarnaik S, Williams S, Amilon C, Wissmar J, Berggren A; HESTIA1 Investigators. A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study. Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2.
PMID: 30187935
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Ticagrelor
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