<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/NCT03254485</url>
  </required_header>
  <id_info>
    <org_study_id>C1973-204</org_study_id>
    <nct_id>NCT03254485</nct_id>
  </id_info>
  <brief_title>A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)</brief_title>
  <acronym>CAPACITY-HFpEF</acronym>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of Different Doses of IW-1973 Over 12 Weeks in Patients With Heart Failure With Preserved Ejection Fraction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akebia Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cyclerion Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Akebia Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973&#xD;
      compared with placebo when administered daily for approximately 12 weeks to patients with&#xD;
      HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in&#xD;
      patients with HFpEF, with or without permanent or persistent atrial fibrillation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2017</start_date>
  <completion_date type="Actual">August 19, 2019</completion_date>
  <primary_completion_date type="Actual">August 19, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs</measure>
    <time_frame>Day 1 up to Day 113</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Ventilatory Efficiency at Week 12</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CPET Responders at Week 12</measure>
    <time_frame>At Week 12</time_frame>
    <description>CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">196</enrollment>
  <condition>Heart Failure With Preserved Ejection Fraction</condition>
  <arm_group>
    <arm_group_label>IW-1973 High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo to match experimental drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IW-1973</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>IW-1973 High Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient is an ambulatory male or female ≥45 years old at the Screening Visit&#xD;
&#xD;
          2. Patient has heart failure with ejection fraction (EF) of ≥40%&#xD;
&#xD;
          3. Patient has a peak VO2 measuring &lt;80% of age- and sex-adjusted normal values&#xD;
&#xD;
          4. Patient has evidence in medical history supporting clinical heart failure syndrome&#xD;
             consisting of at least 1 of the following:&#xD;
&#xD;
               1. Hospitalization or emergency department visit for heart failure within the past&#xD;
                  year&#xD;
&#xD;
               2. Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic&#xD;
                  peptide (NT-proBNP) within the past 6 months&#xD;
&#xD;
               3. Echocardiographic evidence within the past 12 months of at least 2 of the&#xD;
                  following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or&#xD;
                  diastolic dysfunction&#xD;
&#xD;
               4. Hemodynamic evidence of elevated filling pressures&#xD;
&#xD;
          5. Patient meets at least 2 of the following criteria at the Screening Visit:&#xD;
&#xD;
               1. Diagnosis of type 2 diabetes mellitus or prediabetes&#xD;
&#xD;
               2. History of hypertension&#xD;
&#xD;
               3. Body mass index (BMI) &gt;30 kg/m2&#xD;
&#xD;
               4. Age ≥70 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has had acute coronary syndrome or percutaneous coronary intervention within&#xD;
             30 days before Randomization&#xD;
&#xD;
          2. Patient has had cardiac transplantation or has cardiac transplantation planned during&#xD;
             the study&#xD;
&#xD;
          3. Patient has had cardiac artery bypass graft, cardiac mechanical support implantation,&#xD;
             or other cardiac surgery in the 3 months before the Screening Visit or planned during&#xD;
             the study&#xD;
&#xD;
          4. Patient has severe chronic obstructive coronary disease as defined by chronic oxygen&#xD;
             dependence&#xD;
&#xD;
          5. Patient had had heart failure hospitalization with discharge within 30 days before the&#xD;
             Screening Visit&#xD;
&#xD;
          6. Patient has a history of clinically significant hypersensitivity or allergies to any&#xD;
             of the inactive ingredients contained in the active or placebo drug products&#xD;
&#xD;
          7. Patient has previously received IW-1973 in a study, or received an investigational&#xD;
             drug during the 30 days or 5 half lives of that investigational drug (whichever is&#xD;
             longer) before the Screening Visit, or is planning to receive another investigational&#xD;
             drug at any time during the study&#xD;
&#xD;
          8. Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific&#xD;
             inhibitors of PDE5, any supplements for the treatment of erectile dysfunction,&#xD;
             riociguat, or nitrates or nitric oxide (NO) donors in any form&#xD;
&#xD;
          9. Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors&#xD;
&#xD;
         10. Women of childbearing potential must have a negative pregnancy test prior to&#xD;
             randomization and must agree to use protocol-specified contraception from the&#xD;
             Screening Visit through 60 days after the final dose of study drug&#xD;
&#xD;
         11. Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the&#xD;
             Screening Visit or confirmed via sperm analysis) or must agree to use&#xD;
             protocol-specified contraception from the Screening Visit through 60 days after the&#xD;
             final dose of study drug&#xD;
&#xD;
         12. Other exclusion criteria per protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jelena Seferovic, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Cyclerion Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Arrhythmia Research Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiology and Medicine Clinic</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEHM</name>
      <address>
        <city>La Mesa</city>
        <state>California</state>
        <zip>91941</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axis Clinical Trials</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEHM</name>
      <address>
        <city>National City</city>
        <state>California</state>
        <zip>91950</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Clinical Trials</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harbor UCLA Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Denver Cardiology</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Denver Cardiology Associates</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Generation of Medical Research</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Coast Institute for Research</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PCRS Network, LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broward Research Center</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Progressive Medical Research</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Regional Medical Center</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unity Point Health - Methodist Hospital</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscan Physician Network - Indiana Heart Physicians</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lousiana Heart Center</name>
      <address>
        <city>Bogalusa</city>
        <state>Louisiana</state>
        <zip>70427</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston University School of Medicine</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Clinic</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Heart</name>
      <address>
        <city>Ypsilanti</city>
        <state>Michigan</state>
        <zip>48197</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Healthcare John Cochran Medical Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Valley Hospital</name>
      <address>
        <city>Ridgewood</city>
        <state>New Jersey</state>
        <zip>07450</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center (OSUMC)</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProMedica Toledo Hospital</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Oklahoma Heart Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newton Clinical Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73159</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oklahoma Heart Institute</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University (OHSU)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth, Sacred Heart Physicians</name>
      <address>
        <city>Springfield</city>
        <state>Oregon</state>
        <zip>97477</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Institute of Lancaster General Health</name>
      <address>
        <city>Lancaster</city>
        <state>Pennsylvania</state>
        <zip>17602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Drexel University College of Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Dallas Research Associates</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Health Research and Education Insitute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Family Medicine Associates</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schnitzler Cardiovascular Consultants</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University Medical College of Virginia</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Madigan Army Medical Center</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unity Point Health</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin - Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ecogene-21</name>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <zip>G7H 7K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS de l'Estrie - CHUS</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1G 2E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie De Quebec</name>
      <address>
        <city>Québec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <results_first_submitted>August 18, 2022</results_first_submitted>
  <results_first_submitted_qc>August 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 15, 2022</results_first_posted>
  <disposition_first_submitted>August 18, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>February 2, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 5, 2021</disposition_first_posted>
  <last_update_submitted>August 18, 2022</last_update_submitted>
  <last_update_submitted_qc>August 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Failure</keyword>
  <keyword>Cardiovascular</keyword>
  <keyword>HF</keyword>
  <keyword>HFpEF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Praliciguat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03254485/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03254485/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of different doses of praliciguat (IW-1973) compared with placebo in participants with heart failure with preserved ejection fraction (HFpEF).</recruitment_details>
      <pre_assignment_details>A total of 196 participants were enrolled in the study. Participants enrolled under protocol amendment 2 (or earlier) were randomized in a 1:1:1:1 ratio to 10 milligrams (mg) praliciguat, 20 mg praliciguat, 40 mg praliciguat, or placebo. Participants enrolled under protocol amendment 3 were randomized in a 1:1 ratio to either 40 mg praliciguat or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
        </group>
        <group group_id="P2">
          <title>Praliciguat 10 mg</title>
          <description>Participants were randomized to receive praliciguat 10 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="P3">
          <title>Praliciguat 20 mg</title>
          <description>Participants were randomized to receive praliciguat 20 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="P4">
          <title>Praliciguat 40 mg</title>
          <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="90"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-To-Treat (ITT) Population: The ITT Population consisted of all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
        </group>
        <group group_id="B2">
          <title>Praliciguat 10 mg</title>
          <description>Participants were randomized to receive praliciguat 10 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="B3">
          <title>Praliciguat 20 mg</title>
          <description>Participants were randomized to receive praliciguat 20 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="B4">
          <title>Praliciguat 40 mg</title>
          <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="90"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="7"/>
            <count group_id="B4" value="92"/>
            <count group_id="B5" value="196"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.1" spread="9.0"/>
                    <measurement group_id="B2" value="67.3" spread="9.6"/>
                    <measurement group_id="B3" value="69.1" spread="4.6"/>
                    <measurement group_id="B4" value="70.8" spread="9.1"/>
                    <measurement group_id="B5" value="70.3" spread="8.9"/>
                  </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="40"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="35"/>
                    <measurement group_id="B5" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="57"/>
                    <measurement group_id="B5" value="113"/>
                  </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="20"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="72"/>
                    <measurement group_id="B5" value="155"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="72"/>
                    <measurement group_id="B5" value="148"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.</description>
        <time_frame>Day 1 up to Day 113</time_frame>
        <population>Safety Population consisted of all randomized participants who took at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
          </group>
          <group group_id="O2">
            <title>Praliciguat 10 mg</title>
            <description>Participants were randomized to receive praliciguat 10 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
          <group group_id="O3">
            <title>Praliciguat 20 mg</title>
            <description>Participants were randomized to receive praliciguat 20 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
          <group group_id="O4">
            <title>Praliciguat 40 mg</title>
            <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.</description>
          <population>Safety Population consisted of all randomized participants who took at least 1 dose of study drug.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="90"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Study drug-related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12</title>
        <description>Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>Evaluable Population consisted of all participants in the modified (m)ITT population who completed 8 weeks of dosing (±3 days) and had at least 1 evaluable post-Baseline assessment and did not have a dose reduction. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
          </group>
          <group group_id="O2">
            <title>Praliciguat 40 mg</title>
            <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12</title>
          <description>Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min</description>
          <population>Evaluable Population consisted of all participants in the modified (m)ITT population who completed 8 weeks of dosing (±3 days) and had at least 1 evaluable post-Baseline assessment and did not have a dose reduction. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
          <units>mL O2/kg/min</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" lower_limit="-0.49" upper_limit="0.56"/>
                    <measurement group_id="O2" value="-0.26" lower_limit="-0.83" upper_limit="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.3681</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.95</ci_lower_limit>
            <ci_upper_limit>0.35</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12</title>
        <description>6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
          </group>
          <group group_id="O2">
            <title>Praliciguat 40 mg</title>
            <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12</title>
          <description>6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.</description>
          <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
          <units>Meters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.12" lower_limit="26.12" upper_limit="90.11"/>
                    <measurement group_id="O2" value="41.38" lower_limit="8.25" upper_limit="74.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.2817</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-16.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-47.38</ci_lower_limit>
            <ci_upper_limit>13.90</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Ventilatory Efficiency at Week 12</title>
        <description>Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
          </group>
          <group group_id="O2">
            <title>Praliciguat 40 mg</title>
            <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Ventilatory Efficiency at Week 12</title>
          <description>Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.</description>
          <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
          <units>VE/VCO2 Slope</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.564" lower_limit="-0.780" upper_limit="1.908"/>
                    <measurement group_id="O2" value="0.267" lower_limit="-1.118" upper_limit="1.652"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.6508</p_value>
            <method>ANCOVA</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.297</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.591</ci_lower_limit>
            <ci_upper_limit>0.997</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CPET Responders at Week 12</title>
        <description>CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.</description>
        <time_frame>At Week 12</time_frame>
        <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
          </group>
          <group group_id="O2">
            <title>Praliciguat 40 mg</title>
            <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
          </group>
        </group_list>
        <measure>
          <title>CPET Responders at Week 12</title>
          <description>CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.</description>
          <population>Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug (Day 1) up to Follow-up Visit (Day 113)</time_frame>
      <desc>TEAEs, defined as those AEs that started or worsened in severity after the initiation of study drug administration are reported for the Safety Population which consisted of all randomized participants who took at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants were randomized to receive matching placebo orally for 12 weeks: 2 weeks of twice daily (BID) dosing followed by 10 weeks of once daily (QD) dosing.</description>
        </group>
        <group group_id="E2">
          <title>Praliciguat 10 mg</title>
          <description>Participants were randomized to receive praliciguat 10 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="E3">
          <title>Praliciguat 20 mg</title>
          <description>Participants were randomized to receive praliciguat 20 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
        <group group_id="E4">
          <title>Praliciguat 40 mg</title>
          <description>Participants were randomized to receive praliciguat 40 mg orally for 12 weeks: 2 weeks of BID dosing followed by 10 weeks of QD dosing.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDra 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="90"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Coronary artery restenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chondrocalcinosis pyrophosphate</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic foot</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDra 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="90"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="68" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Increased tendency to bruise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Anaemia macrocytic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Diarrhoea haemorrhagic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Therapeutic response unexpected</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="8" subjects_affected="7" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastroenteritis clostridial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary tract infection fungal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Infected skin ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Anaemia postoperative</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Post-traumatic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Postoperative ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Traumatic haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood chloride decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Globulins decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Red blood cell sedimentation rate increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Transferrin saturation decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urine analysis abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urine leukocyte esterase positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Breath sounds abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Mean cell volume increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Venous pressure jugular increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Glucose tolerance impaired</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypercreatininaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Costochondritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acoustic neuroma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Bladder transitional cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypergammaglobulinaemia benign monoclonal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Skin cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="9" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cervical radiculopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Aura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Disorientation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pica</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary hesitation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Balanoposthitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Rales</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dry throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Diabetic foot</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Sinus operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="9" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Arterioenteric fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to changes in study objectives and design (protocol amendment 3), all efficacy analyses was performed using only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis. For completeness, participants treated with both 10 mg and 20 mg praliciguat are included in the AE summaries for safety analyses, as well as for Participant Flow and Baseline Characteristics.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Akebia Therapeutics</name_or_title>
      <organization>Akebia Therapeutics</organization>
      <phone>6178446128</phone>
      <email>trials@akebia.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03254485
org study id: C1973-204
nct id: NCT03254485
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973
      compared with placebo when administered daily for approximately 12 weeks to patients with
      HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in
      patients with HFpEF, with or without permanent or persistent atrial fibrillation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs
time frame: Day 1 up to Day 113
description: An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.
measure: Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12
time frame: Baseline and Week 12
description: Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min
measure: Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12
time frame: Baseline and Week 12
description: 6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.
measure: Change From Baseline in Ventilatory Efficiency at Week 12
time frame: Baseline and Week 12
description: Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.
measure: CPET Responders at Week 12
time frame: At Week 12
description: CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.
arm group label: IW-1973 High Dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo to match experimental drug
intervention type: Drug
intervention name: IW-1973
description: Oral Tablet
arm group label: IW-1973 High Dose
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Oral Tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Jelena Seferovic, MD PhD
role: Study Director
affiliation: Cyclerion Therapeutics, Inc.
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Praliciguat
sharing ipd: No
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reported events: 
certain agreements: 
limitations and caveats: Due to changes in study objectives and design (protocol amendment 3), all efficacy analyses was performed using only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis. For completeness, participants treated with both 10 mg and 20 mg praliciguat are included in the AE summaries for safety analyses, as well as for Participant Flow and Baseline Characteristics.
point of contact: 