<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/NCT01696643</url>
  </required_header>
  <id_info>
    <org_study_id>2402-006</org_study_id>
    <secondary_id>5945-SOIC-12-05</secondary_id>
    <nct_id>NCT01696643</nct_id>
  </id_info>
  <brief_title>Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation</brief_title>
  <official_title>Phase 3 Study to Evaluate the Long-Term Safety and Tolerability of CB-5945 for the Treatment of Opioid-Induced Constipation in Adults Taking Opioid Therapy for Chronic Non-Cancer Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cubist Pharmaceuticals LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cubist Pharmaceuticals LLC</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the long-term safety and tolerability of CB-5945 for&#xD;
      the treatment of opioid-induced constipation (OIC) in adults taking opioid therapy for&#xD;
      chronic non-cancer pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, double-blind, placebo-controlled, parallel-group study in participants&#xD;
      with OIC taking opioid therapy for chronic non-cancer pain. Approximately 1,400 participants&#xD;
      (approximately 700 participants per treatment group) with OIC will be randomized at&#xD;
      approximately 225 study centers to receive either 0.25 milligrams (mg) CB-5945 twice daily&#xD;
      (BID) or a matching placebo BID for the 52-week double-blind treatment period, followed by a&#xD;
      4-week follow-up period. All randomized participants will be evaluated for safety,&#xD;
      tolerability, and quality of life from the first dose of study drug through Week 56.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    A review of blinded data indicates that the number of participant exposures needed to reach ICH&#xD;
    standards has been met&#xD;
  </why_stopped>
  <start_date type="Actual">October 12, 2012</start_date>
  <completion_date type="Actual">July 21, 2014</completion_date>
  <primary_completion_date type="Actual">July 21, 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Baseline through Week 56</time_frame>
    <description>A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included &quot;possibly related&quot; or &quot;related&quot; as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52</measure>
    <time_frame>Baseline, Weeks 49-52</time_frame>
    <description>Throughout the study, participants were asked to record changes in maintenance opioid consumption and use of opioid analgesics for breakthrough or exacerbation of pain in a paper diary. Opioid consumption (including rescue opioids) of each participant was converted to an oral morphine-equivalent total daily dose (METDD). Opioid consumption (in milligrams of METDD) was summarized in 4-week intervals. The change from baseline to Weeks 49-52 is summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52</measure>
    <time_frame>Baseline, Week 52</time_frame>
    <description>The PAC-QOL questionnaire contains a total of 28 items, each rated within 4 subscales: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each item was rated on a 5-point Likert scale with the following score definitions, depending on the question: 0 = not at all (or none of the time), 1 = a little bit (or a little of the time), 2 = moderately (or some of the time), 3 = quite a bit (or most of the time), and 4 = extremely (or all of the time). The total score is the mean of all non-missing items. The range of the total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). Negative change from baseline values indicate improvement in constipation quality of life. Each participant completed the PAC-QOL at Baseline and Week 52 using a 2-week recall period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52</measure>
    <time_frame>Baseline, Week 52</time_frame>
    <description>The PCSA asked participants to rate the severity of their overall constipation during the 24 hours prior to the assessment, using a scale of 0 to 10, where 0 is no constipation and 10 is the worst constipation imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Trough Concentrations of CB-5945</measure>
    <time_frame>Weeks 4, 12, 24, 36, and 52</time_frame>
    <description>Blood samples for trough concentrations of CB-5945 were collected before the participant's morning dose of study drug at Weeks 4, 12, 24, 36, and 52. Overall concentration was based on the mean trough level for each participant across all weeks.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events</measure>
    <time_frame>Baseline through Week 56</time_frame>
    <description>Cardiovascular (CV) events of interested included mycardial infarction, unstable angina, CV accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.&#xD;
Gastrointestinal (GI) events of interest included emergency department visits for the serious adverse events of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.&#xD;
Central opioid withdrawal (OW) events of interest included opioid withdrawal syndrome. The adverse events that indicated central OW included, but were not limited to, hyperhidrosis, tremor, dysphoria, and myalgia.&#xD;
The number of participants with at least 1 confirmed CV, GI, or Central OW event is presented.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1407</enrollment>
  <condition>Opioid-Induced Constipation</condition>
  <arm_group>
    <arm_group_label>CB-5945</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, administered orally, BID for 52 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CB-5945</intervention_name>
    <arm_group_label>CB-5945</arm_group_label>
    <other_name>Bevenopran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is taking a stable daily dose of opioids of ≥30-mg morphine-equivalent total daily&#xD;
             dose (METDD) for chronic non-cancer pain&#xD;
&#xD;
          -  Has constipation that is caused by the chronic use of opioids&#xD;
&#xD;
          -  Is willing to use only the study-provided laxative(s) and to discontinue use of all&#xD;
             other laxatives, enemas, stool softeners, and other medications to treat constipation&#xD;
             (for example, lubiprostone) during the study period (from Screening until the last&#xD;
             study assessment).&#xD;
&#xD;
          -  Is able and willing to refrain from facilitating defecation via manual maneuvers (for&#xD;
             example, digital evacuation or support of the pelvic floor) during the study period&#xD;
             (from Screening to the last study assessment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has gastrointestinal (GI) or pelvic disorders known to affect bowel transit (for&#xD;
             example, obstruction) or contribute to bowel dysfunction&#xD;
&#xD;
          -  Has evidence of intestinal obstruction&#xD;
&#xD;
          -  Has a history of rectal bleeding not due to hemorrhoids or fissures&#xD;
&#xD;
          -  Has an active malignancy of any type (participants with a history of successfully&#xD;
             treated malignancy &gt;5 years before the scheduled administration of study medication&#xD;
             and participants with treated basal or squamous cell cancer may be enrolled)&#xD;
&#xD;
          -  Is taking antispasmodics (for example, dicyclomine), antidiarrheals (for example,&#xD;
             loperamide), prokinetics (for example, metoclopramide), or locally acting chloride&#xD;
             channel activators (for example, lubiprostone)&#xD;
&#xD;
          -  Is taking non-opioid medications known to cause constipation (for example, iron&#xD;
             sulfate therapy or tricyclic antidepressants)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Cubist Pharmaceuticals LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Canada</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <results_first_submitted>July 14, 2015</results_first_submitted>
  <results_first_submitted_qc>August 27, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 28, 2015</results_first_posted>
  <last_update_submitted>October 17, 2018</last_update_submitted>
  <last_update_submitted_qc>October 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Opioid</keyword>
  <keyword>Constipation</keyword>
  <keyword>Chronic</keyword>
  <keyword>Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</mesh_term>
    <mesh_term>Opioid-Induced Constipation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CB-5945</title>
          <description>0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo, administered orally, BID for 52 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="703"/>
                <participants group_id="P2" count="704"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="701"/>
                <participants group_id="P2" count="702">2 participants randomized to placebo took CB-5945. Their results are included in the CB-5945 group.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="174"/>
                <participants group_id="P2" count="169"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="529"/>
                <participants group_id="P2" count="535"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="67"/>
                <participants group_id="P2" count="67"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="286"/>
                <participants group_id="P2" count="294"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="142"/>
                <participants group_id="P2" count="149"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant on Restricted Bed Rest</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Site Error</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant Incarcerated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Medical Monitor Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant Did Not Receive Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>CB-5945</title>
          <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo, administered orally, BID for 52 weeks</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="703"/>
            <count group_id="B2" value="700"/>
            <count group_id="B3" value="1403"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.5" spread="10.00"/>
                    <measurement group_id="B2" value="53.9" spread="10.21"/>
                    <measurement group_id="B3" value="54.2" spread="10.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="437"/>
                    <measurement group_id="B2" value="417"/>
                    <measurement group_id="B3" value="854"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="266"/>
                    <measurement group_id="B2" value="283"/>
                    <measurement group_id="B3" value="549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="676"/>
                    <measurement group_id="B2" value="649"/>
                    <measurement group_id="B3" value="1325"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="117"/>
                    <measurement group_id="B2" value="122"/>
                    <measurement group_id="B3" value="239"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="563"/>
                    <measurement group_id="B2" value="555"/>
                    <measurement group_id="B3" value="1118"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="677"/>
                    <measurement group_id="B2" value="672"/>
                    <measurement group_id="B3" value="1349"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included &quot;possibly related&quot; or &quot;related&quot; as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.</description>
        <time_frame>Baseline through Week 56</time_frame>
        <population>All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included &quot;possibly related&quot; or &quot;related&quot; as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.</description>
          <population>All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="700"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Had at least 1 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.5"/>
                    <measurement group_id="O2" value="54.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Had at least 1 drug-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.9"/>
                    <measurement group_id="O2" value="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinued treatment due to a TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0"/>
                    <measurement group_id="O2" value="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52</title>
        <description>Throughout the study, participants were asked to record changes in maintenance opioid consumption and use of opioid analgesics for breakthrough or exacerbation of pain in a paper diary. Opioid consumption (including rescue opioids) of each participant was converted to an oral morphine-equivalent total daily dose (METDD). Opioid consumption (in milligrams of METDD) was summarized in 4-week intervals. The change from baseline to Weeks 49-52 is summarized.</description>
        <time_frame>Baseline, Weeks 49-52</time_frame>
        <population>All randomized participants who received at least 1 dose of study drug and had evaluable METDD data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52</title>
          <description>Throughout the study, participants were asked to record changes in maintenance opioid consumption and use of opioid analgesics for breakthrough or exacerbation of pain in a paper diary. Opioid consumption (including rescue opioids) of each participant was converted to an oral morphine-equivalent total daily dose (METDD). Opioid consumption (in milligrams of METDD) was summarized in 4-week intervals. The change from baseline to Weeks 49-52 is summarized.</description>
          <population>All randomized participants who received at least 1 dose of study drug and had evaluable METDD data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>milligrams of METDD</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="672"/>
                <count group_id="O2" value="664"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.456" spread="90.2190"/>
                    <measurement group_id="O2" value="-12.297" spread="88.8681"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52</title>
        <description>The PAC-QOL questionnaire contains a total of 28 items, each rated within 4 subscales: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each item was rated on a 5-point Likert scale with the following score definitions, depending on the question: 0 = not at all (or none of the time), 1 = a little bit (or a little of the time), 2 = moderately (or some of the time), 3 = quite a bit (or most of the time), and 4 = extremely (or all of the time). The total score is the mean of all non-missing items. The range of the total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). Negative change from baseline values indicate improvement in constipation quality of life. Each participant completed the PAC-QOL at Baseline and Week 52 using a 2-week recall period.</description>
        <time_frame>Baseline, Week 52</time_frame>
        <population>All randomized participants who received at least 1 dose of study drug and had evaluable PAC-QOL data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52</title>
          <description>The PAC-QOL questionnaire contains a total of 28 items, each rated within 4 subscales: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each item was rated on a 5-point Likert scale with the following score definitions, depending on the question: 0 = not at all (or none of the time), 1 = a little bit (or a little of the time), 2 = moderately (or some of the time), 3 = quite a bit (or most of the time), and 4 = extremely (or all of the time). The total score is the mean of all non-missing items. The range of the total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). Negative change from baseline values indicate improvement in constipation quality of life. Each participant completed the PAC-QOL at Baseline and Week 52 using a 2-week recall period.</description>
          <population>All randomized participants who received at least 1 dose of study drug and had evaluable PAC-QOL data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>units on a 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="240"/>
                <count group_id="O2" value="236"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.63" spread="0.699"/>
                    <measurement group_id="O2" value="-0.45" spread="0.583"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52</title>
        <description>The PCSA asked participants to rate the severity of their overall constipation during the 24 hours prior to the assessment, using a scale of 0 to 10, where 0 is no constipation and 10 is the worst constipation imaginable.</description>
        <time_frame>Baseline, Week 52</time_frame>
        <population>All randomized participants who received at least 1 dose of study drug and had evaluable PCSA data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52</title>
          <description>The PCSA asked participants to rate the severity of their overall constipation during the 24 hours prior to the assessment, using a scale of 0 to 10, where 0 is no constipation and 10 is the worst constipation imaginable.</description>
          <population>All randomized participants who received at least 1 dose of study drug and had evaluable PCSA data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>units on a 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="208"/>
                <count group_id="O2" value="193"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="3.24"/>
                    <measurement group_id="O2" value="-2.2" spread="3.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Trough Concentrations of CB-5945</title>
        <description>Blood samples for trough concentrations of CB-5945 were collected before the participant's morning dose of study drug at Weeks 4, 12, 24, 36, and 52. Overall concentration was based on the mean trough level for each participant across all weeks.</description>
        <time_frame>Weeks 4, 12, 24, 36, and 52</time_frame>
        <population>All participants randomized to CB-5945 who received at least 1 dose of study drug and had evaluable CB-5945 concentration data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Trough Concentrations of CB-5945</title>
          <description>Blood samples for trough concentrations of CB-5945 were collected before the participant's morning dose of study drug at Weeks 4, 12, 24, 36, and 52. Overall concentration was based on the mean trough level for each participant across all weeks.</description>
          <population>All participants randomized to CB-5945 who received at least 1 dose of study drug and had evaluable CB-5945 concentration data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>picograms per milliliter (pg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="631"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4 (n=615)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="517.51" spread="403.391"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=522)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="549.66" spread="425.131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=419)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="547.31" spread="453.548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=288)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="573.57" spread="517.118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52 (n=203)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="616.57" spread="725.849"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall (n=631)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="517.19" spread="375.963"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events</title>
        <description>Cardiovascular (CV) events of interested included mycardial infarction, unstable angina, CV accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.&#xD;
Gastrointestinal (GI) events of interest included emergency department visits for the serious adverse events of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.&#xD;
Central opioid withdrawal (OW) events of interest included opioid withdrawal syndrome. The adverse events that indicated central OW included, but were not limited to, hyperhidrosis, tremor, dysphoria, and myalgia.&#xD;
The number of participants with at least 1 confirmed CV, GI, or Central OW event is presented.</description>
        <time_frame>Baseline through Week 56</time_frame>
        <population>All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>CB-5945</title>
            <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, administered orally, BID for 52 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events</title>
          <description>Cardiovascular (CV) events of interested included mycardial infarction, unstable angina, CV accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.&#xD;
Gastrointestinal (GI) events of interest included emergency department visits for the serious adverse events of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.&#xD;
Central opioid withdrawal (OW) events of interest included opioid withdrawal syndrome. The adverse events that indicated central OW included, but were not limited to, hyperhidrosis, tremor, dysphoria, and myalgia.&#xD;
The number of participants with at least 1 confirmed CV, GI, or Central OW event is presented.</description>
          <population>All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="700"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CV event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GI event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Central OW event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.</desc>
      <group_list>
        <group group_id="E1">
          <title>CB-5945</title>
          <description>0.25 mg CB-5945, administered orally, BID for 52 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo, administered orally, BID for 52 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Faecaloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Mallory-Weiss syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pancreatitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Empyema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Enteritis infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lobar pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Infected bites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Meningitis staphylococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypovolaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Arthropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer in situ</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ovarian neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Benign anorectal neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Uterine leiomyoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="417"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Violence-related symptom</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Peripheral vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 15.1</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="403" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="373" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haemorrhagic Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Iron Deficiency Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Normochromic Normocytic Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Atrioventricular Block First Degree</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cardiac Failure Congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cyanosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinus Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ventricular Extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Angina Unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen Impaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Otorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Deafness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypogonadism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Adrenal Mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Androgen Deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypogonadism Male</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="283"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation Increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blindness Unilateral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Eye Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Eyelid Ptosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Panophthalmitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Conjunctival Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Iritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="90" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="51" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Lower</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rectal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Colonic Polyp</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Faecal Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Frequent Bowel Movements</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Wall Mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Anorectal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Aphthous Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bowel Movement Irregularity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dental Caries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Erosive Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Faecaloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Faeces Discoloured</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Food Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastric Polyps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastric Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gingival Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hiatus Hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oral Papule</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Peptic Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rectal Discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abdominal Adhesions</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Abnormal Faeces</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diverticulum Intestinal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Inguinal Hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rectal Spasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Salivary Hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Withdrawal Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chest Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Influenza Like Illness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Medical Device Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Adverse Drug Reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Feeling Cold</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Spinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Temperature Intolerance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Face Oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hepatic Mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hepatic Steatosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Liver Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Biliary Dilatation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal Allergy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Allergy To Arthropod Bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Allergy To Metals</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Allergy To Vaccine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tooth Abscess</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ear Infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oral Candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pharyngitis Streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Atypical Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Eye Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Localised Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Staphylococcal Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tooth Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Viral Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vulvovaginal Mycotic Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bronchopneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cellulitis Of Male External Genital Organ</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="266"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="283"/>
              </event>
              <event>
                <sub_title>Chronic Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ear Infection Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastritis Viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Viral Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Herpes Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Impetigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Infected Bites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Kidney Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Otitis Externa</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Papilloma Viral Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinusitis Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Staphylococcal Skin Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vaginitis Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Viral Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Acute Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chlamydial Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fungal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Norovirus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Genital Herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Herpes Simplex</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lower Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oesophageal Candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Skin Candida</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Subcutaneous Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tinea Pedis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Wound Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ligament Sprain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Muscle Strain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Arthropod Bite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Foot Fracture</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Head Injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Dislocation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Procedural Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tendon Rupture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Accidental Exposure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hand Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Heat Exhaustion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ligament Rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Limb Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lip Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Meniscus Lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rib Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Road Traffic Accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Suture Rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tendon Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tooth Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Upper Limb Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Wrist Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Anaemia Postoperative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Anal Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Burns Second Degree</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pneumothorax Traumatic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Weight Increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Creatine Phosphokinase Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Lactate Dehydrogenase Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Pressure Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Uric Acid Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gamma-Glutamyltransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haemoglobin Decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hepatic Enzyme Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Platelet Count Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Aortic Bruit</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Cholesterol Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Glucose Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Sodium Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Triglycerides Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Glomerular Filtration Rate Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematocrit Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Heart Rate Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Liver Function Test Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Monocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Red Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Urine Phosphorus Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Phosphorus Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Sodium Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Testosterone Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blood Urine Present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cardiac Murmur</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Crystal Urine Present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Electrocardiogram Qt Prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fungal Test Positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Glomerular Filtration Rate Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematocrit Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Heart Rate Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Transaminases Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercholesterolaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diabetes Mellitus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypouricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Type 2 Diabetes Mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vitamin D Deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Iron Deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Metabolic Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Obesity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Swelling</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Exostosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Foot Deformity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rheumatoid Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rotator Cuff Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Temporomandibular Joint Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bunion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Flank Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Intervertebral Disc Degeneration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Intervertebral Disc Protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Contracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Instability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pain In Jaw</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Synovial Cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Torticollis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Fibromyalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Groin Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Joint Range Of Motion Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Muscle Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Osteochondrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Plantar Fasciitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Spinal Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Spondylitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Trigger Finger</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Thyroid Neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Colon Adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hepatic Neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Basal Cell Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Breast Cancer Metastatic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinus Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Neuropathy Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Restless Legs Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tension Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Carpal Tunnel Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Complex Regional Pain Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diabetic Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Drooling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hyperaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Migraine With Aura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Mononeuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Narcolepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Occipital Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Parkinson's Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Peroneal Nerve Palsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Speech Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cognitive Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lumbar Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Muscle Contractions Involuntary</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Radiculitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tarsal Tunnel Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Attention Deficit/Hyperactivity Disorder</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Mood Swings</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Affective Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Alcoholism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Stress</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Generalised Anxiety Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Initial Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Panic Attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sleep Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Tobacco Withdrawal Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diabetic Nephropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypertonic Bladder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pyuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Renal Failure Acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Renal Impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nocturia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Polyuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Renal Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian Cyst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Breast Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Breast Mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Endometriosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Genital Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Vaginal Lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Benign Prostatic Hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="283"/>
              </event>
              <event>
                <sub_title>Dysfunctional Uterine Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="417"/>
              </event>
              <event>
                <sub_title>Erectile Dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="283"/>
              </event>
              <event>
                <sub_title>Prostatomegaly</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="266"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="283"/>
              </event>
              <event>
                <sub_title>Vaginal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="437"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="417"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Chronic Obstructive Pulmonary Disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sinus Congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Allergic Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Bronchial Hyperreactivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dyspnoea Exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Lung Hyperinflation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rhinitis Seasonal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Yawning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nasal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Nasal Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Paranasal Sinus Hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Sleep Apnoea Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Cold Sweat</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dermatitis Contact</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Actinic Keratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dermatitis Allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Increased Tendency To Bruise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Ingrowing Nail</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Night Sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pain Of Skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Piloerection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Precancerous Skin Lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Rash Erythematous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Skin Irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Swelling Face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Xeroderma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Dermatitis Atopic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Diabetic Foot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Pruritus Generalised</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Skin Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth Extraction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hot Flush</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Raynaud's Phenomenon</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis Superficial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Aortic Aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Hypertensive Crisis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Peripheral Vascular Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </event>
              <event>
                <sub_title>Post Thrombotic Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="703"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="700"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Vice President, Clinical Research</name_or_title>
      <organization>Cubist Pharmaceuticals</organization>
      <phone>1.781.860.8660</phone>
    </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/NCT01696643
org study id: 2402-006
secondary id: 5945-SOIC-12-05
nct id: NCT01696643
lead sponsor: 
The purpose of this study is to evaluate the long-term safety and tolerability of CB-5945 for
      the treatment of opioid-induced constipation (OIC) in adults taking opioid therapy for
      chronic non-cancer pain.
This is a multicenter, double-blind, placebo-controlled, parallel-group study in participants
      with OIC taking opioid therapy for chronic non-cancer pain. Approximately 1,400 participants
      (approximately 700 participants per treatment group) with OIC will be randomized at
      approximately 225 study centers to receive either 0.25 milligrams (mg) CB-5945 twice daily
      (BID) or a matching placebo BID for the 52-week double-blind treatment period, followed by a
      4-week follow-up period. All randomized participants will be evaluated for safety,
      tolerability, and quality of life from the first dose of study drug through Week 56.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: Baseline through Week 56
description: A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included "possibly related" or "related" as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
measure: Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52
time frame: Baseline, Weeks 49-52
description: Throughout the study, participants were asked to record changes in maintenance opioid consumption and use of opioid analgesics for breakthrough or exacerbation of pain in a paper diary. Opioid consumption (including rescue opioids) of each participant was converted to an oral morphine-equivalent total daily dose (METDD). Opioid consumption (in milligrams of METDD) was summarized in 4-week intervals. The change from baseline to Weeks 49-52 is summarized.
measure: Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52
time frame: Baseline, Week 52
description: The PAC-QOL questionnaire contains a total of 28 items, each rated within 4 subscales: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each item was rated on a 5-point Likert scale with the following score definitions, depending on the question: 0 = not at all (or none of the time), 1 = a little bit (or a little of the time), 2 = moderately (or some of the time), 3 = quite a bit (or most of the time), and 4 = extremely (or all of the time). The total score is the mean of all non-missing items. The range of the total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). Negative change from baseline values indicate improvement in constipation quality of life. Each participant completed the PAC-QOL at Baseline and Week 52 using a 2-week recall period.
measure: Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52
time frame: Baseline, Week 52
description: The PCSA asked participants to rate the severity of their overall constipation during the 24 hours prior to the assessment, using a scale of 0 to 10, where 0 is no constipation and 10 is the worst constipation imaginable.
measure: Plasma Trough Concentrations of CB-5945
time frame: Weeks 4, 12, 24, 36, and 52
description: Blood samples for trough concentrations of CB-5945 were collected before the participant's morning dose of study drug at Weeks 4, 12, 24, 36, and 52. Overall concentration was based on the mean trough level for each participant across all weeks.
measure: Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events
time frame: Baseline through Week 56
description: Cardiovascular (CV) events of interested included mycardial infarction, unstable angina, CV accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.
Gastrointestinal (GI) events of interest included emergency department visits for the serious adverse events of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.
Central opioid withdrawal (OW) events of interest included opioid withdrawal syndrome. The adverse events that indicated central OW included, but were not limited to, hyperhidrosis, tremor, dysphoria, and myalgia.
The number of participants with at least 1 confirmed CV, GI, or Central OW event is presented.
arm group label: CB-5945
arm group type: Experimental
description: 0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, administered orally, BID for 52 weeks
intervention type: Drug
intervention name: CB-5945
arm group label: CB-5945
other name: Bevenopran
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Cubist Pharmaceuticals LLC
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Constipation
mesh term: Opioid-Induced Constipation
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 