<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/NCT03012646</url>
  </required_header>
  <id_info>
    <org_study_id>RIN-PH-203</org_study_id>
    <nct_id>NCT03012646</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of Inhaled Treprostinil in Adult PH Due to COPD</brief_title>
  <official_title>A Prospective, Multicenter, Single-arm Study to Evaluate the Safety and Tolerability of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease</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, single-arm trial to evaluate the safety and efficacy of inhaled&#xD;
      treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with&#xD;
      Chronic Obstructive Pulmonary Disease (COPD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Business decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2017</start_date>
  <completion_date type="Anticipated">April 2019</completion_date>
  <primary_completion_date type="Anticipated">April 2019</primary_completion_date>
  <phase>Phase 2</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>Incidence of Adverse Events Among Participants through 48 Weeks</measure>
    <time_frame>48 weeks</time_frame>
    <description>The incidence of adverse events among participants throughout the 48-week study will be measured by the number of participants analyzed and the percentage of those participants who experienced an adverse event.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in 6-minute Walk Distance (6MWD) from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Forced Expiratory Volume (FEV1) in One Second from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Forced Vital Capacity (FVC) from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Lung Diffusion Capacity (DLCO) from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in right ventricular ejection fraction (RVEF) as assessed via cMRI from Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pulmonary Hypertension</condition>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Active Inhaled Treprostinil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled Treprostinil</intervention_name>
    <description>Inhaled treprostinil (6 mcg/breath) administered four times daily</description>
    <arm_group_label>Active Inhaled Treprostinil</arm_group_label>
    <other_name>Tyvaso</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of WHO Group 3 PH associated with COPD&#xD;
&#xD;
          2. Subjects are required to have a right heart catheterization (RHC) within one year&#xD;
             prior to the first dose of study drug with the following parameters:&#xD;
&#xD;
               1. Pulmonary vascular resistance (PVR) ≥ 4 Wood Units (WU) and&#xD;
&#xD;
               2. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge&#xD;
                  pressure (PCWP) of ≤ 12 mmHg if PVR ≥ 4 WU to &lt; 6.25 WU or ≤ 15 mmHg if PVR ≥&#xD;
                  6.25 WU and&#xD;
&#xD;
               3. A mean pulmonary arterial pressure (mPAP) of ≥ 30 mmHg&#xD;
&#xD;
          3. Clinical Diagnosis of COPD will be made using accepted Global Initiative for Chronic&#xD;
             Obstructive Lung Disease (GOLD) diagnostic criteria, including Baseline spirometry&#xD;
             with the following documented parameters:&#xD;
&#xD;
               1. FEV1 &lt; 65% predicted, and&#xD;
&#xD;
               2. FEV1/ FVC &lt; 70&#xD;
&#xD;
          4. Baseline 6MWD ≥ 100 meters&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons&#xD;
             other than COPD as outlined in inclusion criterion 3. This would include, but is not&#xD;
             limited to, the concomitant presence of thromboembolic disease (acute or chronic),&#xD;
             untreated or inadequately treated obstructive sleep apnea, connective tissue disease&#xD;
             (including but not limited to systemic sclerosis/scleroderma, or systemic lupus&#xD;
             erythematosus), sarcoidosis, interstitial lung disease,human immunodeficiency virus-1&#xD;
             infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.&#xD;
&#xD;
          2. The subject has received any Food and Drug Administration (FDA)-approved medication&#xD;
             for the treatment of PAH (ie, prostacyclin, prostacyclin receptor agonist, endothelin&#xD;
             receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I],or soluble&#xD;
             guanylate cyclase [sGC] stimulator) within 60 days of the first dose of study drug,&#xD;
             except for acute vasoreactivity testing.&#xD;
&#xD;
          3. The subject has evidence of clinically significant left-sided heart disease as defined&#xD;
             by the following criteria per the most recent assessment:&#xD;
&#xD;
               1. Left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge&#xD;
                  pressure (PCWP) &gt;15 mmHg (or &gt;12 mmHg if pulmonary vascular resistance [PVR] ≥4&#xD;
                  to &lt;6.25 WU)&#xD;
&#xD;
               2. Left ventricular ejection fraction &lt;40% as assessed by either angiography or&#xD;
                  echocardiography.&#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>April 2017</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>April 7, 2017</last_update_submitted>
  <last_update_submitted_qc>April 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Treprostinil</keyword>
  <keyword>PH</keyword>
  <keyword>COPD</keyword>
  <keyword>6 Minute Walk Test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <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>
  <!-- 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/NCT03012646
org study id: RIN-PH-203
nct id: NCT03012646
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, single-arm trial to evaluate the safety and efficacy of inhaled
      treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with
      Chronic Obstructive Pulmonary Disease (COPD).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events Among Participants through 48 Weeks
time frame: 48 weeks
description: The incidence of adverse events among participants throughout the 48-week study will be measured by the number of participants analyzed and the percentage of those participants who experienced an adverse event.
measure: Change in 6-minute Walk Distance (6MWD) from Baseline to Week 48
time frame: Baseline and Week 48
measure: Change in plasma concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 48
time frame: Baseline and Week 48
measure: Change in Forced Expiratory Volume (FEV1) in One Second from Baseline to Week 48
time frame: Baseline and Week 48
measure: Change in Forced Vital Capacity (FVC) from Baseline to Week 48
time frame: Baseline and Week 48
measure: Change in Lung Diffusion Capacity (DLCO) from Baseline to Week 48
time frame: Baseline and Week 48
measure: Change in right ventricular ejection fraction (RVEF) as assessed via cMRI from Baseline to Week 48
time frame: Baseline and Week 48
arm group label: Active Inhaled Treprostinil
arm group type: Experimental
description: Active Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.
intervention type: Drug
intervention name: Inhaled Treprostinil
description: Inhaled treprostinil (6 mcg/breath) administered four times daily
arm group label: Active Inhaled Treprostinil
other name: Tyvaso
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Treprostinil