<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/NCT03775421</url>
  </required_header>
  <id_info>
    <org_study_id>AC-055H302</org_study_id>
    <secondary_id>2018-002821-45</secondary_id>
    <nct_id>NCT03775421</nct_id>
  </id_info>
  <brief_title>An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients.</brief_title>
  <acronym>RUBATO OL</acronym>
  <official_title>Prospective, Multi-center, Single-arm, Open-label Long-term Study Assessing the Safety, Tolerability, and Effectiveness of Macitentan in Fontan-palliated Adult and Adolescent Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Actelion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Covance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Henry Ford Health System</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Almac Clinical Technologies</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ActiGraph LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medidata Solutions</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Actelion</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this open-label (OL) trial is to study the long-term use of macitentan for up to 2&#xD;
      years in Fontan-palliated adult and adolescent patients beyond the 52 weeks of treatment in&#xD;
      the parent RUBATO double-blind (DB) study (AC-055H301, NCT03153137). This OL trial studies&#xD;
      the long-term effect of macitentan in Fontan-palliated patients as it is not known if the&#xD;
      effect of macitentan is sustained beyond 52 weeks (end of the parent RUBATO DB study). In&#xD;
      addition, the trial also studies the long-term safety of macitentan as this is also unknown.&#xD;
      Furthermore, the opportunity will be given to patients who were on placebo in the parent&#xD;
      RUBATO DB study to receive macitentan 10 mg and benefit from a potentially active treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    As The RUBATO DB study (NCT03153137) did not show any benefit of treatment with macitentan in&#xD;
    Fontan-palliated participants, the sponsor has decided to terminate the RUBATO OL study&#xD;
    (NCT03775421). No new safety observations were made.&#xD;
  </why_stopped>
  <start_date type="Actual">April 11, 2019</start_date>
  <completion_date type="Actual">January 18, 2022</completion_date>
  <primary_completion_date type="Actual">January 18, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study is designed as an open-label (OL), single-arm, multicenter long-term trial in which all adolescent (≥ 12 years) and adult male and female subjects who had previously completed in the parent RUBATO DB study (AC-055H301, NCT03153137) will enroll. The primary objective of the study is to assess the long-term safety and tolerability of macitentan. All efficacy endpoints including the ones listed below are considered as exploratory in nature.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events (TEAEs)</measure>
    <time_frame>Up to 133 weeks</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Serious AEs (TESAEs)</measure>
    <time_frame>Up to 133 weeks</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With TEAEs Leading to Death</measure>
    <time_frame>Up to 133 weeks</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment</measure>
    <time_frame>Up to 133 weeks</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation</measure>
    <time_frame>Up to 133 weeks</time_frame>
    <description>Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. &gt;=:greater than or equal to; &gt;:greater than; &lt;:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Hemoglobin Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in hemoglobin over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Hematocrit Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in hematocrit over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Pulse Rate Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in pulse rate over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in SpO2 over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Body Weight Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in body weight over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Glomerular Filtration Rate (GFR) Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in GFR over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Prothrombin Time Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in prothrombin time over time was reported in this outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Prothrombin International Normalized Ratio Over Time</measure>
    <time_frame>Baseline up to Week 130</time_frame>
    <description>Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)</measure>
    <time_frame>Baseline, Week 52, and Week 104</time_frame>
    <description>Change from baseline in peak VO2 was reported in this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)</measure>
    <time_frame>Baseline, Week 26, Week 52, Week 78, and Week 104</time_frame>
    <description>Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Congenital Heart Disease With Fontan Circulation</condition>
  <arm_group>
    <arm_group_label>Open-label treatment period</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral administration of 10 mg macitentan once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>macitentan 10 mg</intervention_name>
    <description>macitentan 10 mg, film-coated tablet, oral use</description>
    <arm_group_label>Open-label treatment period</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent/assent from the subject and/or a legal representative prior&#xD;
             to initiation of any study-mandated procedures.&#xD;
&#xD;
          -  Subjects who have completed Week 52 of the parent AC-055H301/RUBATO DB study&#xD;
             (NCT03153137)&#xD;
&#xD;
          -  Women of childbearing potential must:&#xD;
&#xD;
               1. have a negative serum pregnancy test prior to first intake of OL study drug, and,&#xD;
&#xD;
               2. agree to perform monthly pregnancy tests up to the end of the safety follow up&#xD;
                  (S-FU) period, and,&#xD;
&#xD;
               3. use reliable methods of contraception from enrollment up to at least 30 days&#xD;
                  after study treatment discontinuation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical worsening leading to medical interventions including reoperation of Fontan&#xD;
             circulation (Fontan take-down) during the enrollment period&#xD;
&#xD;
          -  Systolic blood pressure &lt; 90 mmHg (&lt; 85 mmHg for subjects &lt; 18 years old and &lt; 150 cm&#xD;
             of height) at rest&#xD;
&#xD;
          -  Criteria related to macitentan use&#xD;
&#xD;
          -  Any known factor or disease that may interfere with treatment compliance or full&#xD;
             participation in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thierry Francis Briand, MD</last_name>
    <role>Study Director</role>
    <affiliation>Actelion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital Heart Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Medical Research Providence Health Care</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Prince Charles Hospital, Adult Congenital Heart Disease Unit</name>
      <address>
        <city>Chermside</city>
        <zip>4032</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital</name>
      <address>
        <city>Parkville</city>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Québec Université Laval</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 4G2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Anzhen Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Children's Medical Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice v Motole</name>
      <address>
        <city>Praha 5</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet Kardiologisk Klinisk</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker - Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cardiologique Du Haut-Lévêque</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1640</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne</name>
      <address>
        <city>Gdansk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn</name>
      <address>
        <city>Krakow</city>
        <zip>31-202</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Specjalistyczny We Wroclawiu</name>
      <address>
        <city>Wrocław</city>
        <zip>51-124</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <results_first_submitted>January 16, 2023</results_first_submitted>
  <results_first_submitted_qc>March 6, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 7, 2023</results_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Congenital Heart Failure</keyword>
  <keyword>macitentan</keyword>
  <keyword>Univentricular Heart</keyword>
  <keyword>Cavopulmonary Anastomosis</keyword>
  <keyword>Fontan circulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macitentan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03775421/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03775421/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1 participant was enrolled twice with 2 different participant IDs but only 111 participants were enrolled in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Macitentan 10 mg</title>
          <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="111"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Macitentan 10 mg</title>
          <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="111"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.1" spread="7.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More than one race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown or Not Reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>AUSTRALIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CANADA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CHINA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CZECH REPUBLIC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DENMARK</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FRANCE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NEW ZEALAND</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>POLAND</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAIWAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED KINGDOM</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs)</title>
        <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.</description>
        <time_frame>Up to 133 weeks</time_frame>
        <population>The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs)</title>
          <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.</description>
          <population>The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).</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="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Serious AEs (TESAEs)</title>
        <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.</description>
        <time_frame>Up to 133 weeks</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Serious AEs (TESAEs)</title>
          <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</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="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With TEAEs Leading to Death</title>
        <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
        <time_frame>Up to 133 weeks</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With TEAEs Leading to Death</title>
          <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</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="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment</title>
        <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
        <time_frame>Up to 133 weeks</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment</title>
          <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.</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="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation</title>
        <description>Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. &gt;=:greater than or equal to; &gt;:greater than; &lt;:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.</description>
        <time_frame>Up to 133 weeks</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;n&quot; specifies those participants who were analyzed for each specific category.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation</title>
          <description>Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. &gt;=:greater than or equal to; &gt;:greater than; &lt;:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;n&quot; specifies those participants who were analyzed for each specific category.</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="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hemoglobin: LL&lt;100</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: LL (&lt; 75)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: LLL (&lt; 1.9)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: LL (&lt; 3.0)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: HH (&gt; 4.0)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: LL (&lt; 1.5)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PINR: HH (&gt;=1.5 ULN)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PINR: HHH (&gt;= 2.5 ULN)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase: HH (&gt;=3 ULN)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: HH (&gt;=2 ULN)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase: HH (&gt; 2.5 ULN)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GFR: LL (&lt; 60)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose: LL (&lt; 3.0)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose: HH (&gt; 8.9)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium: HH (&gt;5.5)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium: LLL (&lt;130)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Triglycerides: HH (&gt;3.42)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Hemoglobin Over Time</title>
        <description>Change from baseline in hemoglobin over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (overall number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hemoglobin Over Time</title>
          <description>Change from baseline in hemoglobin over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (overall number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>g/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.0" spread="9.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="9.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.0" spread="7.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="10.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="19.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Hematocrit Over Time</title>
        <description>Change from baseline in hematocrit over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematocrit Over Time</title>
          <description>Change from baseline in hematocrit over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>Liters/Liter (L/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.016" spread="0.0323"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.007" spread="0.0288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.011" spread="0.0247"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.008" spread="0.0285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.010" spread="0.0624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time</title>
        <description>Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time</title>
          <description>Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>10^9 cells/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Leukocytes: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.358" spread="1.2966"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.222" spread="1.3677"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.300" spread="1.2868"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.255" spread="1.2914"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.560" spread="1.1186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.185" spread="1.0712"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.074" spread="1.0624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.233" spread="1.0569"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.105" spread="1.1060"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.400" spread="1.0130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.153" spread="0.3176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.098" spread="0.5366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.016" spread="0.3046"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.089" spread="0.3181"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.113" spread="0.2223"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.2" spread="24.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.3" spread="30.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.1" spread="24.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.1" spread="25.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="12.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time</title>
        <description>Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time</title>
          <description>Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>millimeters of mercury (mmHg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic BP: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="13.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic BP: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="14.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic BP: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="14.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic BP: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="6.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic BP: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12" spread="8.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic BP: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="12.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic BP: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="12.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic BP: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="11.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic BP: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="9.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic BP: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="7.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Pulse Rate Over Time</title>
        <description>Change from baseline in pulse rate over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pulse Rate Over Time</title>
          <description>Change from baseline in pulse rate over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>beats per minute (bpm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="10.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="10.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="10.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="8.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="13.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time</title>
        <description>Change from baseline in SpO2 over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time</title>
          <description>Change from baseline in SpO2 over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>percentage of SpO2 (%)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="2.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="2.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="2.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Body Weight Over Time</title>
        <description>Change from baseline in body weight over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Body Weight Over Time</title>
          <description>Change from baseline in body weight over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>kilograms (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="4.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="3.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="4.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="5.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time</title>
        <description>Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time</title>
          <description>Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALT: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="8.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="10.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" spread="11.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.8" spread="15.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.7" spread="23.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="8.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="9.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="11.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.1" spread="17.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.3" spread="41.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AP: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.7" spread="36.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AP: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="25.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AP: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.6" spread="28.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AP: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.8" spread="53.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AP: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="6.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="14.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="15.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="18.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.2" spread="18.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="13.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time</title>
        <description>Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time</title>
          <description>Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>micromoles per liter (mcmol/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Bilirubin: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="6.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="10.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="5.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="6.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="9.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="9.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="8.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="8.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="5.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Glomerular Filtration Rate (GFR) Over Time</title>
        <description>Change from baseline in GFR over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Glomerular Filtration Rate (GFR) Over Time</title>
          <description>Change from baseline in GFR over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>milliliters/minute/1.73 meter square</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="15.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="15.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="13.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="17.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Prothrombin Time Over Time</title>
        <description>Change from baseline in prothrombin time over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Prothrombin Time Over Time</title>
          <description>Change from baseline in prothrombin time over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.31" spread="3.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="4.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.38" spread="2.293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.12" spread="3.317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.57" spread="0.651"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Prothrombin International Normalized Ratio Over Time</title>
        <description>Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.</description>
        <time_frame>Baseline up to Week 130</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Prothrombin International Normalized Ratio Over Time</title>
          <description>Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.401"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.456"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.12" spread="0.245"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="0.379"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 130</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.07" spread="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)</title>
        <description>Change from baseline in peak VO2 was reported in this outcome measure.</description>
        <time_frame>Baseline, Week 52, and Week 104</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)</title>
          <description>Change from baseline in peak VO2 was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>Milliliters per kilogram per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.82" spread="2.724"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.93" spread="1.968"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)</title>
        <description>Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.</description>
        <time_frame>Baseline, Week 26, Week 52, Week 78, and Week 104</time_frame>
        <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Macitentan 10 mg</title>
            <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)</title>
          <description>Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.</description>
          <population>The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, &quot;N&quot; (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; &quot;n&quot; specifies those participants who were analyzed at specified timepoints.</population>
          <units>mean count per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.74" spread="131.622"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.58" spread="153.196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 78</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.14" spread="165.965"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-62.87" spread="189.264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 133 weeks</time_frame>
      <desc>The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).</desc>
      <group_list>
        <group group_id="E1">
          <title>Macitentan 10 mg</title>
          <description>Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 24.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Atrial Flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </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="111"/>
              </event>
              <event>
                <sub_title>Colitis Ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Incarcerated Inguinal Hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Covid-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anastomotic Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Sperm Concentration Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Spermatozoa Progressive Motility Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral Disc Protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hepatocellular Carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Clonic Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Abortion Spontaneous</sub_title>
                <description>This data was not corresponding to a study participant but the female partner of a male participant.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Mental Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA Version 24.0</default_vocab>
        <default_assessment>Non-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="34" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Covid-19</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="111"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="111"/>
              </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="4" subjects_at_risk="111"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="111"/>
              </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>If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 30 days before submission for publication or presentation.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was stopped prematurely by the sponsor because the main double-blind (DB) study (AC-055H301; NCT03153137) did not meet the primary and secondary efficacy outcome measures.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Senior Clinical Leader PH</name_or_title>
      <organization>Actelion Pharmaceuticals Ltd</organization>
      <phone>844-434-4210</phone>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT03775421
org study id: AC-055H302
secondary id: 2018-002821-45
nct id: NCT03775421
lead sponsor: 
collaborator: 
collaborator: 
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The aim of this open-label (OL) trial is to study the long-term use of macitentan for up to 2
      years in Fontan-palliated adult and adolescent patients beyond the 52 weeks of treatment in
      the parent RUBATO double-blind (DB) study (AC-055H301, NCT03153137). This OL trial studies
      the long-term effect of macitentan in Fontan-palliated patients as it is not known if the
      effect of macitentan is sustained beyond 52 weeks (end of the parent RUBATO DB study). In
      addition, the trial also studies the long-term safety of macitentan as this is also unknown.
      Furthermore, the opportunity will be given to patients who were on placebo in the parent
      RUBATO DB study to receive macitentan 10 mg and benefit from a potentially active treatment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study is designed as an open-label (OL), single-arm, multicenter long-term trial in which all adolescent (≥ 12 years) and adult male and female subjects who had previously completed in the parent RUBATO DB study (AC-055H301, NCT03153137) will enroll. The primary objective of the study is to assess the long-term safety and tolerability of macitentan. All efficacy endpoints including the ones listed below are considered as exploratory in nature.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
time frame: Up to 133 weeks
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.
measure: Number of Participants With Treatment-emergent Serious AEs (TESAEs)
time frame: Up to 133 weeks
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.
measure: Number of Participants With TEAEs Leading to Death
time frame: Up to 133 weeks
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
measure: Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
time frame: Up to 133 weeks
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
measure: Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
time frame: Up to 133 weeks
description: Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. >=:greater than or equal to; >:greater than; <:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.
measure: Change From Baseline in Hemoglobin Over Time
time frame: Baseline up to Week 130
description: Change from baseline in hemoglobin over time was reported in this outcome measure.
measure: Change From Baseline in Hematocrit Over Time
time frame: Baseline up to Week 130
description: Change from baseline in hematocrit over time was reported in this outcome measure.
measure: Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
time frame: Baseline up to Week 130
description: Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.
measure: Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
time frame: Baseline up to Week 130
description: Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.
measure: Change From Baseline in Pulse Rate Over Time
time frame: Baseline up to Week 130
description: Change from baseline in pulse rate over time was reported in this outcome measure.
measure: Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
time frame: Baseline up to Week 130
description: Change from baseline in SpO2 over time was reported in this outcome measure.
measure: Change From Baseline in Body Weight Over Time
time frame: Baseline up to Week 130
description: Change from baseline in body weight over time was reported in this outcome measure.
measure: Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
time frame: Baseline up to Week 130
description: Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.
measure: Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
time frame: Baseline up to Week 130
description: Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.
measure: Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
time frame: Baseline up to Week 130
description: Change from baseline in GFR over time was reported in this outcome measure.
measure: Change From Baseline in Prothrombin Time Over Time
time frame: Baseline up to Week 130
description: Change from baseline in prothrombin time over time was reported in this outcome measure.
measure: Change From Baseline in Prothrombin International Normalized Ratio Over Time
time frame: Baseline up to Week 130
description: Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.
measure: Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
time frame: Baseline, Week 52, and Week 104
description: Change from baseline in peak VO2 was reported in this outcome measure.
measure: Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
time frame: Baseline, Week 26, Week 52, Week 78, and Week 104
description: Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.
arm group label: Open-label treatment period
arm group type: Experimental
description: oral administration of 10 mg macitentan once daily
intervention type: Drug
intervention name: macitentan 10 mg
description: macitentan 10 mg, film-coated tablet, oral use
arm group label: Open-label treatment period
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Thierry Francis Briand, MD
role: Study Director
affiliation: Actelion
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country: Australia
country: Canada
country: China
country: Czechia
country: Denmark
country: France
country: New Zealand
country: Poland
country: Taiwan
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
mesh term: Macitentan
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was stopped prematurely by the sponsor because the main double-blind (DB) study (AC-055H301; NCT03153137) did not meet the primary and secondary efficacy outcome measures.
point of contact: 