<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/NCT03043651</url>
  </required_header>
  <id_info>
    <org_study_id>TDE-HF-302</org_study_id>
    <nct_id>NCT03043651</nct_id>
  </id_info>
  <brief_title>Open-label Extension of Oral Treprostinil in Subjects With PH Associated With HFpEF</brief_title>
  <official_title>An Open-label Extension Study of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) Associated With Heart Failure With Preserved Ejection Fraction (HFpEF) - A Long-term Follow-up to Study TDE-HF-301</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>United Therapeutics</source>
  <oversight_info>
    <has_dmc>No</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>
      This was an open-label study to evaluate the safety of continued therapy with oral&#xD;
      treprostinil in subjects who completed Study TDE-HF-301. This study provided long-term,&#xD;
      open-label data regarding the effect of continued long-term oral treprostinil therapy for the&#xD;
      treatment of pulmonary hypertension (PH) associated with heart failure with preserved&#xD;
      ejection fraction (HFpEF). Subject visits occurred at Baseline, Weeks 6, 12, 18, 24, and&#xD;
      every 12 weeks thereafter until either oral treprostinil was commercially available to treat&#xD;
      PH associated with HFpEF or the study was discontinued by the Sponsor.&#xD;
&#xD;
      The Sponsor terminated Studies TDE-HF-301 and TDE-HF-302 on 14 October 2019 due to slow&#xD;
      enrollment. Safety data from the final subject in Study TDE-HF-302 were recorded on 02 March&#xD;
      2020. Due to the lower than expected number of subjects enrolled, the planned secondary&#xD;
      efficacy-related endpoints were not analyzed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study TDE-HF-302 was a multicenter, open-label study in subjects participating and completing&#xD;
      all required visits for Study TDE-HF-301. This study assessed the long-term safety of oral&#xD;
      treprostinil in subjects with PH associated with HFpEF.&#xD;
&#xD;
      Subjects received oral treprostinil as 0.125-, 0.25-, 1-, and 2.5-mg sustained-release&#xD;
      tablets. For subjects who were randomly allocated to receive oral treprostinil in Study&#xD;
      TDE-HF-301, the initial dose of oral treprostinil was the same as the final dose in Study&#xD;
      TDE-HF-301. Subjects randomly allocated to receive placebo in Study TDE-HF-301 were&#xD;
      administered the initial dose of oral treprostinil at 0.125 mg 3 times daily (TID). Dose&#xD;
      increases could occur in 0.125-mg increments every 72 hours at the discretion of the&#xD;
      Investigator up to 6 mg TID, the maximum allowable dose determined by the Data Monitoring&#xD;
      Committee during Study TDE-HF-301. Doses of study drug were to be increased in the absence of&#xD;
      dose-limiting drug-related adverse events (AEs) to ensure that each subject received the&#xD;
      optimal dose throughout the study. Subjects returned for visits at Weeks 6, 12, 18, and 24,&#xD;
      and every 12 weeks thereafter. Subjects who terminated the study early were asked to return&#xD;
      to the study center for a final evaluation.&#xD;
&#xD;
      Safety assessments consisted of AEs, clinical laboratory parameters, and clinical assessment&#xD;
      of heart failure signs and symptoms.&#xD;
&#xD;
      Due to the lower than expected number of subjects enrolled, the planned secondary&#xD;
      efficacy-related endpoints were not analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated by Sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">January 30, 2018</start_date>
  <completion_date type="Actual">March 2, 2020</completion_date>
  <primary_completion_date type="Actual">March 2, 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301</measure>
    <time_frame>Baseline through study completion, up to approximately 25 months</time_frame>
    <description>The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Pulmonary Hypertension Associated With HFpEF</condition>
  <arm_group>
    <arm_group_label>Oral treprostinil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sustained-release tablets for TID administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral treprostinil</intervention_name>
    <description>Sustained-release oral tablets for TID administration</description>
    <arm_group_label>Oral treprostinil</arm_group_label>
    <other_name>Treprostinil diethanolamine, Treprostinil diolamine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. The subject participated in Study TDE-HF-301, remained on study drug, was compliant with&#xD;
        study procedures and assessments during Study TDE-HF-301, and completed through Week 24 of&#xD;
        that study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The subject was pregnant or lactating.&#xD;
&#xD;
          2. The subject was prematurely discontinued from Study TDE-HF-301 for any reason.&#xD;
&#xD;
          3. The subject developed a concurrent illness or condition during Study TDE-HF-301,&#xD;
             which, in the opinion of the Investigator, represented a risk to the subject's overall&#xD;
             health if they enrolled in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mardi Gomberg-Maitland, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>George Washington University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner University Medical Center Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Healthcare System of Greater Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Los Angeles Pulmonary Division</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Barbara Cottage Hospital</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Denver Cardiology Associates</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Denver Cardiology</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Faculty Associates, George Washington University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Cardiology Associates</name>
      <address>
        <city>Brandon</city>
        <state>Florida</state>
        <zip>33511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Lung, Sleep, and Critical Care Specialists</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>33204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Florida Pulmonary Group, P.A.</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Hospital</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida ; Tampa General Hospital</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic of Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Physicians Georgia Lung</name>
      <address>
        <city>Austell</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WellStar Medical Group</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advocate Christ Medical Center</name>
      <address>
        <city>Oak Lawn</city>
        <state>Illinois</state>
        <zip>60453</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF HealthCare</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Health Methodist Research Institute, INC</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Heart and Vascular Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46250</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Hospital and Health Services</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>55242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Heart Center</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentuckiana Pulmonary Associates</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville Physicians Outpatient Center</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chest Medicine Associates</name>
      <address>
        <city>South Portland</city>
        <state>Maine</state>
        <zip>04106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Elizabeth's Medical Center</name>
      <address>
        <city>Brighton</city>
        <state>Massachusetts</state>
        <zip>02135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Medical Group</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Hospital</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Hospital of Kansas City</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barnabas Health Lung Center</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical College</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Health Physicians, PC</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asheville Cardiology Associates</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pinehurst Medical Clinic</name>
      <address>
        <city>Pinehurst</city>
        <state>North Carolina</state>
        <zip>28374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lindner Research Center The Christ Hospital Health Network</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toldedo Medical Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oregon Clinic</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lancaster General Hospital</name>
      <address>
        <city>Lancaster</city>
        <state>Pennsylvania</state>
        <zip>17601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AnMed Health Pulmonary and Sleep Medicine</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research - Anderson</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stern Cardiovascular Foundation</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Medical Group</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-2650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Research Institute</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Tech University Health Sciences Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Heart and Vascular Institute</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sentara Cardiovascular Research Institute</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Medical Research Center</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University Hospital</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora St. Luke's Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <results_first_submitted>September 25, 2020</results_first_submitted>
  <results_first_submitted_qc>September 25, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 22, 2020</results_first_posted>
  <last_update_submitted>September 25, 2020</last_update_submitted>
  <last_update_submitted_qc>September 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary Hypertension</keyword>
  <keyword>HFpEF</keyword>
  <keyword>6-Minute Walk Test</keyword>
  <keyword>Oral Treprostinil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Treprostinil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03043651/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>September 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03043651/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Oral Treprostinil</title>
          <description>Sustained-release tablets for TID administration&#xD;
Oral Treprostinil: Sustained-release oral tablets for TID administration</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</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="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All Subjects</population>
      <group_list>
        <group group_id="B1">
          <title>Oral Treprostinil</title>
          <description>Sustained-release tablets for TID administration&#xD;
Oral Treprostinil: Sustained-release oral tablets for TID administration</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76.0" lower_limit="46" upper_limit="85"/>
                  </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="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301</title>
        <description>The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study.</description>
        <time_frame>Baseline through study completion, up to approximately 25 months</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Oral Treprostinil</title>
            <description>Sustained-release tablets for TID administration&#xD;
Oral Treprostinil: Sustained-release oral tablets for TID administration</description>
          </group>
        </group_list>
        <measure>
          <title>Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301</title>
          <description>The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study.</description>
          <population>Safety Population</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="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The study duration was 25 months overall. The study was discontinued by the Sponsor on 14 October 2019 due to slow enrollment in the parent study, TDE-HF-301.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oral Treprostinil</title>
          <description>Sustained-release tablets for TID administration&#xD;
Oral Treprostinil: Sustained-release oral tablets for TID administration</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Normochromic normocytic anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Tachyarrhythmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Gastrointestinal angiectasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pneumonia mycoplasmal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Hypervolaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Hypochloraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="28" subjects_affected="26" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="17" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>N-terminal prohormone brain natriuretic peptide increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="20" subjects_affected="13" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="35" subjects_affected="31" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="48"/>
              </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>Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the study without the prior written consent of the Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Louis Holdstock</name_or_title>
      <organization>United Therapeutics</organization>
      <phone>919-425-8866</phone>
      <email>lholdstock@unither.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/NCT03043651
org study id: TDE-HF-302
nct id: NCT03043651
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This was an open-label study to evaluate the safety of continued therapy with oral
      treprostinil in subjects who completed Study TDE-HF-301. This study provided long-term,
      open-label data regarding the effect of continued long-term oral treprostinil therapy for the
      treatment of pulmonary hypertension (PH) associated with heart failure with preserved
      ejection fraction (HFpEF). Subject visits occurred at Baseline, Weeks 6, 12, 18, 24, and
      every 12 weeks thereafter until either oral treprostinil was commercially available to treat
      PH associated with HFpEF or the study was discontinued by the Sponsor.

      The Sponsor terminated Studies TDE-HF-301 and TDE-HF-302 on 14 October 2019 due to slow
      enrollment. Safety data from the final subject in Study TDE-HF-302 were recorded on 02 March
      2020. Due to the lower than expected number of subjects enrolled, the planned secondary
      efficacy-related endpoints were not analyzed.
Study TDE-HF-302 was a multicenter, open-label study in subjects participating and completing
      all required visits for Study TDE-HF-301. This study assessed the long-term safety of oral
      treprostinil in subjects with PH associated with HFpEF.

      Subjects received oral treprostinil as 0.125-, 0.25-, 1-, and 2.5-mg sustained-release
      tablets. For subjects who were randomly allocated to receive oral treprostinil in Study
      TDE-HF-301, the initial dose of oral treprostinil was the same as the final dose in Study
      TDE-HF-301. Subjects randomly allocated to receive placebo in Study TDE-HF-301 were
      administered the initial dose of oral treprostinil at 0.125 mg 3 times daily (TID). Dose
      increases could occur in 0.125-mg increments every 72 hours at the discretion of the
      Investigator up to 6 mg TID, the maximum allowable dose determined by the Data Monitoring
      Committee during Study TDE-HF-301. Doses of study drug were to be increased in the absence of
      dose-limiting drug-related adverse events (AEs) to ensure that each subject received the
      optimal dose throughout the study. Subjects returned for visits at Weeks 6, 12, 18, and 24,
      and every 12 weeks thereafter. Subjects who terminated the study early were asked to return
      to the study center for a final evaluation.

      Safety assessments consisted of AEs, clinical laboratory parameters, and clinical assessment
      of heart failure signs and symptoms.

      Due to the lower than expected number of subjects enrolled, the planned secondary
      efficacy-related endpoints were not analyzed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301
time frame: Baseline through study completion, up to approximately 25 months
description: The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study.
arm group label: Oral treprostinil
arm group type: Experimental
description: Sustained-release tablets for TID administration
intervention type: Drug
intervention name: Oral treprostinil
description: Sustained-release oral tablets for TID administration
arm group label: Oral treprostinil
other name: Treprostinil diethanolamine, Treprostinil diolamine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Mardi Gomberg-Maitland, MD
role: Principal Investigator
affiliation: George Washington University
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country: United States
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Treprostinil
sharing ipd: No
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