<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/NCT02234141</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-357-1394</org_study_id>
    <secondary_id>2014-002131-34</secondary_id>
    <nct_id>NCT02234141</nct_id>
  </id_info>
  <brief_title>Selonsertib in Adults With Pulmonary Arterial Hypertension</brief_title>
  <acronym>ARROW</acronym>
  <official_title>A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Study of GS-4997 in Subjects With Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the effect of selonsertib (GS-4997) on&#xD;
      pulmonary vascular resistance (PVR), as measured by right heart catheterization (RHC) in&#xD;
      adults with pulmonary arterial hypertension (PAH). The study will consist of a 24-week&#xD;
      placebo-controlled treatment period and a long-term selonsertib treatment period.&#xD;
      Participants completing the 24-week placebo-controlled period will be eligible to receive&#xD;
      active treatment with selonsertib in the long-term treatment period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>mPAP is the mean blood pressure in the pulmonary artery. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>mRAP is the mean blood pressure in the right atrium of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>RVCP is a cardiopulmonary hemodynamic assessment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in 6MWD Test</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in BDI After the 6MWD Test</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number &gt; 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in NT-proBNP</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1</measure>
    <time_frame>Baseline up to Week 24</time_frame>
    <description>TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both &gt; 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>TAPSE is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>TAS is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>RVFAC is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">151</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Selonsertib 2 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Selonsertib 6 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Selonsertib 18 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive selonsertib placebo for 24 weeks, and may then be rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet administered orally once daily</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>GS-4997</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selonsertib</intervention_name>
    <description>Tablets administered orally once daily</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Selonsertib 18 mg</arm_group_label>
    <arm_group_label>Selonsertib 2 mg</arm_group_label>
    <arm_group_label>Selonsertib 6 mg</arm_group_label>
    <other_name>GS-4997</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary&#xD;
             arterial hypertension (HPAH), drug- and toxin-induced PAH, or PAH associated with&#xD;
             connective tissue disease, human immunodeficiency virus (HIV) infection, or congenital&#xD;
             heart defects (repaired greater than 1 year prior to Screening)&#xD;
&#xD;
          -  Meet all of the following hemodynamic criteria by means of a screening right heart&#xD;
             catheterization (RHC) completed prior to randomization:&#xD;
&#xD;
               -  Mean pulmonary artery pressure (mPAP) of greater than or equal to (≥) 25&#xD;
                  millimeters of mercury (mm Hg)&#xD;
&#xD;
               -  Pulmonary vascular resistance (PVR) ≥ 400 dyne* second/centimeter^5&#xD;
                  (dynes*sec/cm^5)&#xD;
&#xD;
               -  Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic&#xD;
                  pressure (LVEDP) of less than or equal to (≤) 12 mm Hg if PVR ≥ 400 and less than&#xD;
                  (&lt;) 500 dynes*sec/cm^5, or PCWP/LVEDP ≤ 15 mm Hg if PVR ≥ 500 dynes•sec/cm^5&#xD;
&#xD;
          -  Be able to walk a distance of at least 100 meters&#xD;
&#xD;
          -  Have World Health Organization (WHO) Functional Class II or III symptoms&#xD;
&#xD;
          -  Meet the following criteria determined by pulmonary function tests completed no more&#xD;
             than 24 weeks prior to screening, performed with or without bronchodilation:&#xD;
&#xD;
               -  Forced expiratory volume in one second (FEV1) ≥ 55 percent (%) of predicted&#xD;
                  normal&#xD;
&#xD;
               -  FEV1: forced vital capacity (FVC) ratio ≥ 0.60&#xD;
&#xD;
          -  Receiving treatment with one or more drugs approved for PAH for ≥ 12 consecutive weeks&#xD;
             and at stable dose for ≥ 8 consecutive weeks&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PAH associated with significant venous or capillary involvement (PCWP&#xD;
             greater than [&gt;] 15 mm Hg), pulmonary capillary hemangiomatosis, portal hypertension,&#xD;
             or unrepaired congenital heart defects&#xD;
&#xD;
          -  Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 NICE classification&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic,&#xD;
             valvular or constrictive heart disease&#xD;
&#xD;
          -  Uncontrolled hypertension (≥ 180/110 mm Hg) at Screening&#xD;
&#xD;
          -  End stage renal disease (receiving peritoneal dialysis, hemodialysis, or status after&#xD;
             renal transplantation)&#xD;
&#xD;
          -  Severe liver disease (Child-Pugh Class C, with or without cirrhosis)&#xD;
&#xD;
        Individuals may be rescreened one additional time with prior notification to and approval&#xD;
        by the sponsor.&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of South Alabama Medical Center</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Lung Disease Institute</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Pulmonary Specialist, Ltd</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona Clinical and Translational Science (CATS) Research Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Greater Los Angeles Healthcare System</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LA Biomedical Research Institute Harbor-UCLA Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cardiac and Vascular Center, Anschutz Inpatient Pavillion</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston University Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary M. Parkes Center // University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martha Morehouse Medical Pavilion</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Presbyterian Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Fairfax Medical Campus</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter Lougheed Center</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver General Hospital, The Lung Centre // Vancouver Coastal Health, Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Victoria Hospital - London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de caridologie et de pneumologie de Quebee (IUCPQ)</name>
      <address>
        <city>Sainte Foy</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble Clinique Universitaire de Pneumologie</name>
      <address>
        <city>Grenoble Cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Bicetre, Service de Pneumologie-Reanimation Respiratoire</name>
      <address>
        <city>Le Kremlin Bicetre Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cardiologique-CHRU Lille, Service de cardiologie</name>
      <address>
        <city>Lille Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikul Giessen und Marburg GmbH</name>
      <address>
        <city>Giessen</city>
        <state>Hessen</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik III fur Innere Medizin, Herzzentrum Uniklinik Koln</name>
      <address>
        <city>Koln</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Leipzig</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg</name>
      <address>
        <city>Regensburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita &quot;Sapienza&quot;-Azienda Policlinico Umberto 1</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VU University Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Doce (12) de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital</name>
      <address>
        <city>Clydebank</city>
        <state>West Dunbartonshire</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hampstead NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Facility, Royal Hallamshrie Hospital</name>
      <address>
        <city>Sheffield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>March 19, 2019</results_first_submitted>
  <results_first_submitted_qc>March 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2019</results_first_posted>
  <disposition_first_submitted>December 21, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>December 21, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">December 23, 2016</disposition_first_posted>
  <last_update_submitted>March 19, 2019</last_update_submitted>
  <last_update_submitted_qc>March 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Selonsertib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at study sites in North America and Europe. The first participant was screened on 12 November 2014. The last study visit occurred on 13 December 2016.</recruitment_details>
      <pre_assignment_details>185 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Selonsertib 2 mg</title>
          <description>Participants were randomized to receive selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1) and may have continued on this dosing during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P2">
          <title>Selonsertib 6 mg</title>
          <description>Participants were randomized to receive selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1) and may have continued on this dosing during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P3">
          <title>Selonsertib 18 mg</title>
          <description>Participants were randomized to receive selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1) and may have continued on this dosing during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Participants were randomized received placebo tablet once daily for 24 weeks (Period 1) and may have been rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P5">
          <title>Placebo to Selonsertib 2 mg</title>
          <description>Participants received placebo in Period 1 and were rerandomized to receive selonsertib 2 mg tablet once daily during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P6">
          <title>Placebo to Selonsertib 6 mg</title>
          <description>Participants received placebo in Period 1 and were rerandomized to receive selonsertib 6 mg tablet once daily during the long-term treatment phase (Period 2).</description>
        </group>
        <group group_id="P7">
          <title>Placebo to Selonsertib 18 mg</title>
          <description>Participants received placebo in Period 1 and were rerandomized to receive selonsertib 18 mg tablet once daily during the long-term treatment phase (Period 2).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period (24 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="38"/>
                <participants group_id="P3" count="37"/>
                <participants group_id="P4" count="37"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="32"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</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 group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator's discretion</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized but not treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Long-Term Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33">2 participants who completed Period 1 did not continue into the Long-Term Treatment Phase.</participants>
                <participants group_id="P2" count="31">1 participant who completed the Period 1 did not continue into the Long-Term Treatment Phase.</participants>
                <participants group_id="P3" count="33">2 participants who completed Period 1 did not continue into the Long-Term Treatment Phase.</participants>
                <participants group_id="P4" count="0">Participants were rerandomized to receive selonsertib during the Long-Term Treatment Phase.</participants>
                <participants group_id="P5" count="10">The Placebo group was rerandomized to receive selonsertib during the Long-Term Treatment Phase.</participants>
                <participants group_id="P6" count="12">The Placebo group was rerandomized to receive selonsertib during the Long-Term Treatment Phase.</participants>
                <participants group_id="P7" count="10">The Placebo group was rerandomized to receive selonsertib during the Long-Term Treatment Phase.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="31"/>
                <participants group_id="P3" count="33"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="12"/>
                <participants group_id="P7" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <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="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator's discretion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Discontinued by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="27"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="10"/>
                <participants group_id="P7" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set included all randomized participants who received greater than or equal to (≥) 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Selonsertib 2 mg</title>
          <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
        </group>
        <group group_id="B2">
          <title>Selonsertib 6 mg</title>
          <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
        </group>
        <group group_id="B3">
          <title>Selonsertib 18 mg</title>
          <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</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="39"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="37"/>
            <count group_id="B4" value="37"/>
            <count group_id="B5" value="150"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50" spread="13.9"/>
                    <measurement group_id="B2" value="49" spread="13.7"/>
                    <measurement group_id="B3" value="48" spread="14.1"/>
                    <measurement group_id="B4" value="55" spread="15.5"/>
                    <measurement group_id="B5" value="50" spread="14.5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="31"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="35"/>
                    <measurement group_id="B5" value="129"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="35"/>
                    <measurement group_id="B5" value="139"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>World Health Organization (WHO) Functional Class</title>
          <description>Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Class II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="90"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Class III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>6-Minute Walk Distance (6MWD) Test</title>
          <description>The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes.</description>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="452" spread="111.9"/>
                    <measurement group_id="B2" value="449" spread="85.3"/>
                    <measurement group_id="B3" value="437" spread="102.7"/>
                    <measurement group_id="B4" value="412" spread="109.3"/>
                    <measurement group_id="B5" value="437" spread="103.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)</title>
          <description>NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function.</description>
          <units>picograms per milliliter (pg/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="385" lower_limit="86" upper_limit="1177"/>
                    <measurement group_id="B2" value="431" lower_limit="174" upper_limit="1134"/>
                    <measurement group_id="B3" value="352" lower_limit="135" upper_limit="822"/>
                    <measurement group_id="B4" value="492" lower_limit="158" upper_limit="1424"/>
                    <measurement group_id="B5" value="412" lower_limit="122" upper_limit="1224"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Borg Dyspnea Index (BDI)</title>
          <description>Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), Any number greater than (&gt;) 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.5" spread="2.13"/>
                    <measurement group_id="B2" value="3.7" spread="2.41"/>
                    <measurement group_id="B3" value="3.5" spread="1.53"/>
                    <measurement group_id="B4" value="3.6" spread="1.94"/>
                    <measurement group_id="B5" value="3.6" spread="2.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Right Ventricular Fractional Area Change (RVFAC)</title>
          <description>RVFAC is an echocardiographic assessment of right ventricular function.</description>
          <population>Participants in the Safety Analysis Set with available data were analyzed.</population>
          <units>percentage of RV area</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="36"/>
                    <count group_id="B3" value="34"/>
                    <count group_id="B4" value="33"/>
                    <count group_id="B5" value="140"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.7" spread="8.00"/>
                    <measurement group_id="B2" value="33.6" spread="9.68"/>
                    <measurement group_id="B3" value="37.3" spread="8.47"/>
                    <measurement group_id="B4" value="32.3" spread="9.59"/>
                    <measurement group_id="B5" value="34.5" spread="9.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tricuspid Annular Plane Systolic Excursion (TAPSE)</title>
          <description>TAPSE is an echocardiographic assessment of right ventricular function.</description>
          <population>Participants in the Safety Analysis Set with available data were analyzed.</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="35"/>
                    <count group_id="B3" value="36"/>
                    <count group_id="B4" value="32"/>
                    <count group_id="B5" value="140"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.5" spread="0.31"/>
                    <measurement group_id="B2" value="1.5" spread="0.37"/>
                    <measurement group_id="B3" value="1.5" spread="0.29"/>
                    <measurement group_id="B4" value="1.5" spread="0.31"/>
                    <measurement group_id="B5" value="1.5" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Right Atrial Pressure (mRAP)</title>
          <description>mRAP is the mean blood pressure in the right atrium of the heart.</description>
          <units>millimeters of mercury (mm Hg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8" spread="4.3"/>
                    <measurement group_id="B2" value="9" spread="4.4"/>
                    <measurement group_id="B3" value="9" spread="4.3"/>
                    <measurement group_id="B4" value="8" spread="3.5"/>
                    <measurement group_id="B5" value="8" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Pulmonary Artery Pressure (mPAP)</title>
          <description>mPAP is the mean blood pressure in the pulmonary artery.</description>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.4" spread="15.28"/>
                    <measurement group_id="B2" value="56.7" spread="10.79"/>
                    <measurement group_id="B3" value="55.0" spread="12.51"/>
                    <measurement group_id="B4" value="51.3" spread="9.94"/>
                    <measurement group_id="B5" value="54.1" spread="12.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pulmonary Vascular Resistance (PVR)</title>
          <description>PVR is a measure of the extent to which pulmonary circulation resists cardiac output.</description>
          <population>Participants in the Safety Analysis Set with available data were analyzed.</population>
          <units>dynes*second/centimeter^5 (dyn*sec/cm^5)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="38"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="149"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="734" spread="313.4"/>
                    <measurement group_id="B2" value="806" spread="381.2"/>
                    <measurement group_id="B3" value="809" spread="366.1"/>
                    <measurement group_id="B4" value="743" spread="268.2"/>
                    <measurement group_id="B5" value="772" spread="333.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cardiac Index</title>
          <description>Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area.</description>
          <units>liters/minute/square meter (L/min/m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="39"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="37"/>
                    <count group_id="B4" value="37"/>
                    <count group_id="B5" value="150"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.87" spread="0.818"/>
                    <measurement group_id="B2" value="2.86" spread="0.679"/>
                    <measurement group_id="B3" value="2.69" spread="0.649"/>
                    <measurement group_id="B4" value="2.64" spread="0.501"/>
                    <measurement group_id="B5" value="2.77" spread="0.674"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)</title>
        <description>PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set (all randomized participants who received ≥ 1 dose of study drug) with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)</title>
          <description>PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set (all randomized participants who received ≥ 1 dose of study drug) with available data were analyzed.</population>
          <units>dyne*sec/cm^5</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35" spread="35.4"/>
                    <measurement group_id="O2" value="-28" spread="30.2"/>
                    <measurement group_id="O3" value="-21" spread="37.9"/>
                    <measurement group_id="O4" value="6" spread="28.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The protocol-specified primary analysis was to compare each selonsertib dose group with the placebo group, using Wilcoxon (van Elteren) test, with respect to change from baseline in PVR at Week 24, stratifying by randomization stratum (the underlying etiology of PAH idiopathic/heritable [yes/no] and the number of background PAH therapies they were receiving {1, 2, or greater than or equal to [≥] 3}).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Nonparametric pairwise comparison</non_inferiority_desc>
            <p_value>= 0.214</p_value>
            <p_value_desc>P-value was calculated using the generalized van Elteren test/van Elteren test (gvE/vE; stratified Wilcoxon rank sum test).</p_value_desc>
            <method>gvE/vE</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The protocol-specified primary analysis was to compare each selonsertib dose group with the placebo group, using Wilcoxon (van Elteren) test, with respect to change from baseline in PVR at Week 24, stratifying by randomization stratum (the underlying etiology of PAH idiopathic/heritable [yes/no] and the number of background PAH therapies they were receiving [1, 2, or ≥ 3]).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Nonparametric pairwise comparison</non_inferiority_desc>
            <p_value>= 0.270</p_value>
            <p_value_desc>P-value was calculated using the generalized van Elteren test/van Elteren test (gvE/vE; stratified Wilcoxon rank sum test).</p_value_desc>
            <method>gvE/vE</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The protocol-specified primary analysis was to compare each selonsertib dose group with the placebo group, using Wilcoxon (van Elteren) test, with respect to change from baseline in PVR at Week 24, stratifying by randomization stratum (the underlying etiology of PAH idiopathic/heritable [yes/no] and the number of background PAH therapies they were receiving [1, 2, or ≥ 3]).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Nonparametric pairwise comparison</non_inferiority_desc>
            <p_value>= 0.604</p_value>
            <p_value_desc>P-value was calculated using the generalized van Elteren test/van Elteren test (gvE/vE; stratified Wilcoxon rank sum test)</p_value_desc>
            <method>gvE/vE</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index</title>
        <description>Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index</title>
          <description>Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>L/min/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.10"/>
                    <measurement group_id="O2" value="0.1" spread="0.09"/>
                    <measurement group_id="O3" value="0.0" spread="0.09"/>
                    <measurement group_id="O4" value="0.0" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP</title>
        <description>mPAP is the mean blood pressure in the pulmonary artery. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP</title>
          <description>mPAP is the mean blood pressure in the pulmonary artery. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="1.3"/>
                    <measurement group_id="O2" value="-1" spread="1.1"/>
                    <measurement group_id="O3" value="-3" spread="1.4"/>
                    <measurement group_id="O4" value="0" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP</title>
        <description>mRAP is the mean blood pressure in the right atrium of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP</title>
          <description>mRAP is the mean blood pressure in the right atrium of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0.5"/>
                    <measurement group_id="O2" value="0" spread="0.7"/>
                    <measurement group_id="O3" value="-1" spread="0.5"/>
                    <measurement group_id="O4" value="1" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)</title>
        <description>SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)</title>
          <description>SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>percentage of oxygen saturation</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.85"/>
                    <measurement group_id="O2" value="0.1" spread="2.13"/>
                    <measurement group_id="O3" value="1.1" spread="2.07"/>
                    <measurement group_id="O4" value="-2.0" spread="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)</title>
        <description>RVCP is a cardiopulmonary hemodynamic assessment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)</title>
          <description>RVCP is a cardiopulmonary hemodynamic assessment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>watts</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.026"/>
                    <measurement group_id="O2" value="0.00" spread="0.024"/>
                    <measurement group_id="O3" value="-0.03" spread="0.028"/>
                    <measurement group_id="O4" value="-0.01" spread="0.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in 6MWD Test</title>
        <description>The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in 6MWD Test</title>
          <description>The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="6.63"/>
                    <measurement group_id="O2" value="3.5" spread="8.27"/>
                    <measurement group_id="O3" value="-15.9" spread="8.01"/>
                    <measurement group_id="O4" value="-15.0" spread="8.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in BDI After the 6MWD Test</title>
        <description>Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number &gt; 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in BDI After the 6MWD Test</title>
          <description>Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number &gt; 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.24"/>
                    <measurement group_id="O2" value="0.1" spread="0.26"/>
                    <measurement group_id="O3" value="0.1" spread="0.23"/>
                    <measurement group_id="O4" value="0.3" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class</title>
        <description>Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class</title>
          <description>Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</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="36"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unchanged</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="28"/>
                    <measurement group_id="O4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in NT-proBNP</title>
        <description>NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in NT-proBNP</title>
          <description>NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17" spread="0.093"/>
                    <measurement group_id="O2" value="1.01" spread="0.093"/>
                    <measurement group_id="O3" value="1.01" spread="0.082"/>
                    <measurement group_id="O4" value="1.25" spread="0.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale</title>
        <description>Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale</title>
          <description>Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0.8"/>
                    <measurement group_id="O2" value="2" spread="0.9"/>
                    <measurement group_id="O3" value="0" spread="0.8"/>
                    <measurement group_id="O4" value="0" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score</title>
        <description>Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score</title>
          <description>Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="1.1"/>
                    <measurement group_id="O2" value="-1" spread="1.2"/>
                    <measurement group_id="O3" value="1" spread="1.1"/>
                    <measurement group_id="O4" value="-1" spread="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test</title>
        <description>HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test</title>
          <description>HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>beats per minute (bpm)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="2.42"/>
                    <measurement group_id="O2" value="0.1" spread="2.52"/>
                    <measurement group_id="O3" value="-3.0" spread="3.07"/>
                    <measurement group_id="O4" value="2.4" spread="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1</title>
        <description>TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both &gt; 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.</description>
        <time_frame>Baseline up to Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1</title>
          <description>TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both &gt; 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.</description>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">NA = Not reached due to insufficient number of events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">NA = Not reached due to insufficient number of events</measurement>
                    <measurement group_id="O3" value="225.0" lower_limit="225.0" upper_limit="225.0"/>
                    <measurement group_id="O4" value="178.0" lower_limit="178.0" upper_limit="NA">NA = Not reached due to insufficient number of events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE</title>
        <description>TAPSE is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE</title>
          <description>TAPSE is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.04"/>
                    <measurement group_id="O2" value="-0.1" spread="0.06"/>
                    <measurement group_id="O3" value="0.0" spread="0.04"/>
                    <measurement group_id="O4" value="0.0" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)</title>
        <description>Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)</title>
          <description>Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>percentage of strain</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="26"/>
                <count group_id="O4" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0.7"/>
                    <measurement group_id="O2" value="2" spread="0.6"/>
                    <measurement group_id="O3" value="-1" spread="0.7"/>
                    <measurement group_id="O4" value="1" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)</title>
        <description>TAS is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)</title>
          <description>TAS is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>centimeters per second (cm/sec)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0.4"/>
                    <measurement group_id="O2" value="0" spread="0.3"/>
                    <measurement group_id="O3" value="0" spread="0.2"/>
                    <measurement group_id="O4" value="0" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)</title>
        <description>The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)</title>
          <description>The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="32"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" spread="0.037"/>
                    <measurement group_id="O2" value="0.05" spread="0.052"/>
                    <measurement group_id="O3" value="0.01" spread="0.021"/>
                    <measurement group_id="O4" value="-0.02" spread="0.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)</title>
        <description>RVFAC is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Selonsertib 2 mg</title>
            <description>Participants received selonsertib 2 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O2">
            <title>Selonsertib 6 mg</title>
            <description>Participants received selonsertib 6 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O3">
            <title>Selonsertib 18 mg</title>
            <description>Participants received selonsertib 18 mg tablet once daily for 24 weeks during the treatment phase (Period 1).</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Participants received placebo tablet once daily for 24 weeks (Period 1).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)</title>
          <description>RVFAC is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.</description>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>percentage of RV area</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.16"/>
                    <measurement group_id="O2" value="0.0" spread="1.23"/>
                    <measurement group_id="O3" value="-1.1" spread="1.25"/>
                    <measurement group_id="O4" value="-0.6" spread="1.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 97 weeks plus 30 days</time_frame>
      <desc>Safety Analysis Set included all randomized participants who received ≥1 dose of study drug. 10, 12, and 10 participants (from Placebo Period 1 arm who were rerandomized to receive study drug) were included in selonsertib 2 mg, selonsertib 6 mg, and selonsertib 18 mg arms, respectively, for the purpose of Adverse Event (AE) data reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Selonsertib 2 mg</title>
          <description>Participants received selonsertib 2 mg for 24 weeks during the treatment phase (Period 1) and during the long-term treatment phase (Period 2). AEs in this reporting group include AEs that occurred in 10 participants who were rerandomized from the Placebo Period 1 group to receive selonsertib 2 mg during the long-term treatment phase.</description>
        </group>
        <group group_id="E2">
          <title>Selonsertib 6 mg</title>
          <description>Participants received selonsertib 6 mg for 24 weeks during the treatment phase (Period 1) and during the long-term treatment phase (Period 2). AEs in this reporting group include AEs that occurred in 12 participants who were rerandomized from the Placebo Period 1 group to receive selonsertib 6 mg during the long-term treatment phase.</description>
        </group>
        <group group_id="E3">
          <title>Selonsertib 18 mg</title>
          <description>Participants received selonsertib 18 mg for 24 weeks during the treatment phase (Period 1) and during the long-term treatment phase (Period 2). AEs in this reporting group include AEs that occurred in 10 participants who were rerandomized from the Placebo Period 1 group to receive selonsertib 18 mg during the long-term treatment phase.</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Participants received placebo tablet once daily for 24 weeks (Period 1). AEs reported in this group only include AEs that occurred during Period 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Haemorrhagic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Right ventricular failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Large intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oesophageal achalasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Infusion site inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hepatomegaly</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Transplant dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device breakage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </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" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </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" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pulmonary arterial hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic arteriosclerosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Shock haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</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="43" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="44" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="34" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Gastrointestinal viral infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="37"/>
              </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>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gilead Clinical Study Information Center</name_or_title>
      <organization>Gilead Sciences</organization>
      <phone>1-833-445-3230 (GILEAD-0)</phone>
      <email>GileadClinicalTrials@gilead.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/NCT02234141
org study id: GS-US-357-1394
secondary id: 2014-002131-34
nct id: NCT02234141
lead sponsor: 
has dmc: Yes
The primary objective of this study is to evaluate the effect of selonsertib (GS-4997) on
      pulmonary vascular resistance (PVR), as measured by right heart catheterization (RHC) in
      adults with pulmonary arterial hypertension (PAH). The study will consist of a 24-week
      placebo-controlled treatment period and a long-term selonsertib treatment period.
      Participants completing the 24-week placebo-controlled period will be eligible to receive
      active treatment with selonsertib in the long-term treatment period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
time frame: Baseline to Week 24
description: PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Cardiac Index
time frame: Baseline to Week 24
description: Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mPAP
time frame: Baseline to Week 24
description: mPAP is the mean blood pressure in the pulmonary artery. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: mRAP
time frame: Baseline to Week 24
description: mRAP is the mean blood pressure in the right atrium of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Mixed Venous Oxygen Saturation (SVO2) (%)
time frame: Baseline to Week 24
description: SVO2 is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Other Cardiopulmonary Hemodynamic Measures: Right Ventricular Cardiac Power (RVCP)
time frame: Baseline to Week 24
description: RVCP is a cardiopulmonary hemodynamic assessment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in 6MWD Test
time frame: Baseline to Week 24
description: The 6MWD test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. It measures the distance a participant is able to walk in a period of six minutes. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in BDI After the 6MWD Test
time frame: Baseline to Week 24
description: Immediately following completion of the 6-minute walk test, participants were asked to assess breathlessness using the BDI score as follows: 0 = no breathlessness, 10 = extremely strong (maximal breathlessness), any number > 10 = Highest possible. Therefore, the minimum for BDI score was 0 and there was no upper bound. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Number of Participants Experiencing Change From Baseline at Week 24 in WHO Functional Class
time frame: Baseline to Week 24
description: Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g., doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most participants also have edema in the feet and ankles as result of right heart failure. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in NT-proBNP
time frame: Baseline to Week 24
description: NT-proBNP is used to detect, diagnose, and evaluate the severity of heart failure. In general, NT-proBNP levels are higher in participants with heart failure than those who have normal heart function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Short Form (SF-36) Physical Functioning Scale
time frame: Baseline to Week 24
description: Quality of life was assessed using the SF-36 questionnaire, a self-administered multi-item survey that asks 36 questions to measure functional health and well-being from the participant's point of view and consists of eight health domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health) as well as 2 summary measures (Physical Health and Mental Health). Data presented are for 1 of the domains only: Physical Functioning. Scores can range from 0 to 100, with a higher score representing a higher level of functioning. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in emPHasis-10 Questionnaire Score
time frame: Baseline to Week 24
description: Quality of life was assessed using the emPHasis-10 questionnaire, a disease-specific self-administered 10-question questionnaire designed for routine assessment of health-related quality of life in pulmonary hypertension. Total score can range from 0 to 50, with higher scores indicating a worse quality of life. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline at Week 24 in Heart Rate Recovery (HRR) After the 6MWD Test
time frame: Baseline to Week 24
description: HRR was assessed after the 6MWD test. The HRR was calculated as the difference between the heart rate measured immediately after completing the 6MWD test and the second heart rate measured 1 minute after the 6MWD test. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Kaplan-Meier Estimate of Time to Clinical Worsening (TTCW) Evaluated in Period 1
time frame: Baseline up to Week 24
description: TTCW was defined as time to the first occurrence of: death (all-cause), hospitalization for worsening pulmonary arterial hypertension (PAH) (any hospitalization for worsening PAH, lung or heart/lung transplant, atrial septostomy, or initiation of continuously infused prostanoid therapy), or disease progression (defined as both > 15% decrease from baseline in 6MWD test and WHO class III or IV symptoms at two consecutive postbaseline clinic visits separated by ≥ 14 days). TTCW was evaluated using Kaplan-Meier estimates.
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: TAPSE
time frame: Baseline to Week 24
description: TAPSE is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Myocardial Strain (%)
time frame: Baseline to Week 24
description: Right ventricular myocardial strain is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Tricuspid Annular Peak Sys Myocard Velocity (TAS)
time frame: Baseline to Week 24
description: TAS is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Tei Index (RVTI)
time frame: Baseline to Week 24
description: The Tei-index is defined as the sum of the isovolumic contraction and the isovolumic relaxation time divided by ejection time, and thus incorporates elements of both systolic and diastolic phases in the assessment of global ventricular function. An increased Tei-index results from ventricular dysfunction and provides prognostic information for a variety of myocardial conditions. The RVTI is a candidate to increase the non-invasive diagnosis of PAH because it reflects the right ventricular function, is easy to assess, and can be estimated in the same session as the echocardiographic PAP. The normal value of the RVTI is 0.28 +/- 0.04. An increased RVTI is associated with either left ventricular diastolic abnormalities or pulmonary hypertension. This score has no bounds. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
measure: Change From Baseline in Echocardiographic Measures of Right Ventricular Function at Week 24: Right Ventricular Fractional Area Change (RVFAC)
time frame: Baseline to Week 24
description: RVFAC is an echocardiographic assessment of right ventricular function. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.
arm group label: Selonsertib 2 mg
arm group type: Experimental
description: Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.
arm group label: Selonsertib 6 mg
arm group type: Experimental
description: Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
arm group label: Selonsertib 18 mg
arm group type: Experimental
description: Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
arm group label: Placebo
arm group type: Experimental
description: Participants will receive selonsertib placebo for 24 weeks, and may then be rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase.
intervention type: Drug
intervention name: Placebo
description: Tablet administered orally once daily
arm group label: Placebo
other name: GS-4997
intervention type: Drug
intervention name: Selonsertib
description: Tablets administered orally once daily
arm group label: Placebo
arm group label: Selonsertib 18 mg
arm group label: Selonsertib 2 mg
arm group label: Selonsertib 6 mg
other name: GS-4997
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: France
country: Germany
country: Italy
country: Netherlands
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
mesh term: Selonsertib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 