<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/NCT02999906</url>
  </required_header>
  <id_info>
    <org_study_id>TDE-PH-313</org_study_id>
    <nct_id>NCT02999906</nct_id>
  </id_info>
  <brief_title>Study to Compare Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension</brief_title>
  <official_title>A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Compare the Efficacy and Safety of Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension</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>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>
      This is a multicenter, randomized (2:1 oral treprostinil: placebo), double-blind,&#xD;
      placebo-controlled study in subjects with Pulmonary Arterial Hypertension (PAH) who are&#xD;
      currently receiving background dual therapy (ambrisentan, tadalafil) for at least 30 days at&#xD;
      randomization for their PAH. Once randomized, subjects will return for 5 study visits up to&#xD;
      Week 28 during the blinded period. After the Week 28 Visit, eligible subjects will transition&#xD;
      to the open-label period of the study for up to 20 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    For business reasons.&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in 6-Minute Walk Distance (6MWD)</measure>
    <time_frame>Baseline to Week 28</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the effects of triple therapy versus dual therapy on the time to clinical worsening</measure>
    <time_frame>Baseline to Week 28</time_frame>
    <description>clinical worsening is defined by 1 of the following:&#xD;
Death (all causes)&#xD;
Hospitalization due to worsening PAH&#xD;
Initiation of long-term parenteral therapy&#xD;
Disease progression&#xD;
Unsatisfactory long-term clinical response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations From Baseline to Week 28</measure>
    <time_frame>Baseline to week 28</time_frame>
    <description>The level of this biomarker of the (NT-proBNP) serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with a Change From Baseline World Health Organization (WHO) Functional Classification at Week 28.</measure>
    <time_frame>Baseline to week 28</time_frame>
    <description>The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 28.</measure>
    <time_frame>Baseline to week 28</time_frame>
    <description>The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 025; high scores indicate more symptoms), Activity (Score 030; low score indicates good functioning) and Quality of Life (025; high scores indicate poor QoL). The sum of these scores equates to the Total score (080). In the CAMPHOR scores, lower scores indicate improvements.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo (sugar pill)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral treprostinil sustained release tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Treprostinil</intervention_name>
    <description>Sustained release oral tablets for three times daily administration</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>treprostinil diethanolamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo (sugar pill) for three times daily oral administration</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>matching placebo (sugar pill)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Between 18 and 79 years of age, inclusive&#xD;
&#xD;
          2. PAH that is idiopathic / heritable, PAH associated with connective tissue disease, HIV&#xD;
             infection, repaired congenital systemic-to-pulmonary shunts (repaired &gt; 1 year), or&#xD;
             appetite suppressant / toxin use&#xD;
&#xD;
          3. Receiving dual therapy (ambrisentan and tadalafil)&#xD;
&#xD;
          4. Previous testing (e.g. right heart catheterization, echocardiography) consistent with&#xD;
             diagnosis of PAH&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Nursing or pregnant&#xD;
&#xD;
          2. PAH due to conditions other than noted in the above inclusion criteria&#xD;
&#xD;
          3. Received PAH-specific drug therapy for &gt;2 years&#xD;
&#xD;
          4. History of uncontrolled sleep apnea, severe liver disease, severe renal impairment,&#xD;
             left sided heart disease, uncontrolled systemic hypertension&#xD;
&#xD;
          5. Participated in an investigational drug or device study within 90 days prior to&#xD;
             signing consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>October 31, 2017</last_update_submitted>
  <last_update_submitted_qc>October 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PAH</keyword>
  <keyword>Oral Treprostinil</keyword>
  <keyword>dual therapy</keyword>
  <keyword>6 Minute Walk Test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Treprostinil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02999906
org study id: TDE-PH-313
nct id: NCT02999906
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, randomized (2:1 oral treprostinil: placebo), double-blind,
      placebo-controlled study in subjects with Pulmonary Arterial Hypertension (PAH) who are
      currently receiving background dual therapy (ambrisentan, tadalafil) for at least 30 days at
      randomization for their PAH. Once randomized, subjects will return for 5 study visits up to
      Week 28 during the blinded period. After the Week 28 Visit, eligible subjects will transition
      to the open-label period of the study for up to 20 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in 6-Minute Walk Distance (6MWD)
time frame: Baseline to Week 28
measure: Compare the effects of triple therapy versus dual therapy on the time to clinical worsening
time frame: Baseline to Week 28
description: clinical worsening is defined by 1 of the following:
Death (all causes)
Hospitalization due to worsening PAH
Initiation of long-term parenteral therapy
Disease progression
Unsatisfactory long-term clinical response
measure: Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations From Baseline to Week 28
time frame: Baseline to week 28
description: The level of this biomarker of the (NT-proBNP) serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 28.
measure: Number of Participants with a Change From Baseline World Health Organization (WHO) Functional Classification at Week 28.
time frame: Baseline to week 28
description: The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
measure: Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 28.
time frame: Baseline to week 28
description: The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 025; high scores indicate more symptoms), Activity (Score 030; low score indicates good functioning) and Quality of Life (025; high scores indicate poor QoL). The sum of these scores equates to the Total score (080). In the CAMPHOR scores, lower scores indicate improvements.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo (sugar pill)
arm group label: Active
arm group type: Active Comparator
description: Oral treprostinil sustained release tablet
intervention type: Drug
intervention name: Oral Treprostinil
description: Sustained release oral tablets for three times daily administration
arm group label: Active
other name: treprostinil diethanolamine
intervention type: Drug
intervention name: Placebo
description: Placebo (sugar pill) for three times daily oral administration
arm group label: Placebo
other name: matching placebo (sugar pill)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
mesh term: Treprostinil
sharing ipd: No