<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/NCT01728220</url>
  </required_header>
  <id_info>
    <org_study_id>IK-7002-COPD-201</org_study_id>
    <nct_id>NCT01728220</nct_id>
  </id_info>
  <brief_title>Two-Part Dose-Confirming Study of Pulsed Inhaled Nitric Oxide in Subjects With WHO Group 3 Pulmonary Hypertension Associated With COPD</brief_title>
  <official_title>A Placebo-Controlled, Double-Blind, Parallel, Randomized, Two-Part, Clinical Dose-Confirming Study Of Pulsed, Inhaled Nitric Oxide (iNO) In Subjects With World Health Organization (WHO) Group 3 Pulmonary Hypertension (PH) Associated With Chronic Obstructive Pulmonary Disease (COPD) On Long Term Oxygen Therapy (LTOT) INHALE 1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bellerophon Pulse Technologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bellerophon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a placebo-controlled, double-blind, parallel, randomized, two-part, dose-confirming&#xD;
      clinical study characterizing the pharmacodynamic effects of pulsed iNO using the combination&#xD;
      product, inhaled nitric oxide/INOpulse DS-C vs. placebo in subjects with World Health&#xD;
      Organization (WHO) Group 3 pulmonary hypertension (PH) associated with Chronic Obstructive&#xD;
      Pulmonary Disease (COPD) on Long Term Oxygen Therapy (LTOT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This two-part study is designed to confirm the dose of inhaled nitric oxide (NO),&#xD;
      administered through an investigational pulsed delivery device (INOpulse® DS-C) that results&#xD;
      in decreased pulmonary arterial systolic pressure (PASP) without significantly affecting&#xD;
      systemic oxygenation.&#xD;
&#xD;
      In Part A, 80 subjects will be randomized to 1of 4 treatment groups in a 1:1:1:1 ratio (with&#xD;
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed&#xD;
      iNO at a dose of 0.003 mg/kg IBW/hr, 0.010 mg/kg IBW/hr, or 0.015 mg/kg IBW/hr, with a set&#xD;
      pulse width (PW) of 260 milliseconds (ms). Part A subjects assigned to the placebo group will&#xD;
      receive nitrogen (N2) at a randomly assigned device setting of 0.003, 0.010 or 0.015 mg/kg&#xD;
      IBW/hr with a set PW of 260 ms.&#xD;
&#xD;
      Subjects who were randomized in Part A are permitted to participate in Part B of the study.&#xD;
      Subjects will need to be re-screened and re-randomized for Part B participation.&#xD;
&#xD;
      In Part B, 60 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (with&#xD;
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed&#xD;
      iNO at either 0.030 mg/kg IBW/hr or 0.075 mg/kg IBW/hr, with a set PW of 260 ms. Part B&#xD;
      subjects assigned to placebo will receive N2 at a randomly assigned device setting of 0.030&#xD;
      mg/kg IBW/hr or 0.075 mg/kg IBW/hr with a set PW of 260 ms.&#xD;
&#xD;
      Part B will use a skewed block randomization scheme with 10 blocks of 6 subjects as follows:&#xD;
&#xD;
        -  Blocks 1-3: 3 subjects at 0.030 mg/kg IBW/hr, 1 subject at 0.075 mg/kg IBW/hr, and 2&#xD;
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr&#xD;
&#xD;
        -  Blocks 4-7: 2 subjects at 0.030 mg/kg IBW/hr, 2 subjects at 0.075 mg/kg IBW/hr, and 2&#xD;
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr&#xD;
&#xD;
        -  Blocks 8-10: 1 subject at 0.030 mg/kg IBW/hr, 3 subjects at 0.075 mg/kg IBW/hr, and 2&#xD;
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO (measured by 2D transthoracic echocardiography with Doppler)</measure>
    <time_frame>baseline to end of treatment (1 day)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The secondary outcome is the occurrence of a decrease ≥ 5 mm Hg of partial pressure of oxygen in arterial blood (PaO2) from Baseline after treatment with iNO</measure>
    <time_frame>baseline to end of treatment (1 day)</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">159</enrollment>
  <condition>Pulmonary Hypertension</condition>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Inhaled NO delivered via INOpulse DS-C Device</intervention_name>
    <description>Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.</description>
    <arm_group_label>Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)</arm_group_label>
    <arm_group_label>Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_label>Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_label>Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)</arm_group_label>
    <arm_group_label>Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Placebo delivered via INOpulse DS-C Device</intervention_name>
    <description>Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.</description>
    <arm_group_label>Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)</arm_group_label>
    <arm_group_label>Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Former smokers with at least 10 pack-years of tobacco cigarette smoking history before&#xD;
             study entry and who have stopped smoking ≥ 1 month prior to enrollment&#xD;
&#xD;
          2. Age ≥ 40 years, ≤ 80 years&#xD;
&#xD;
          3. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung&#xD;
             Disease (GOLD) criteria&#xD;
&#xD;
          4. A post-bronchodilatory forced expiratory volume in 1 second/forced vital capacity&#xD;
             (FEV1/FVC) &lt; 0.7 and a FEV1 &lt; 60% predicted (values obtained within 6 months prior to&#xD;
             screening can be used unless obtained within ± 7 days of an exacerbation; otherwise,&#xD;
             the test must be performed during screening)&#xD;
&#xD;
          5. Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history&#xD;
&#xD;
          6. Echocardiogram with technical adequacy demonstrating tricuspid regurgitation velocity&#xD;
             (TRV) ≥ 2.9 m/s at Screening, as determined by a blinded central echocardiography&#xD;
             laboratory&#xD;
&#xD;
          7. Females of childbearing potential must have a negative pre-treatment urine pregnancy&#xD;
             test&#xD;
&#xD;
          8. Signed informed consent prior to the initiation of any study mandated procedures or&#xD;
             assessments&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        Subjects who meet any of the following criteria are not eligible for enrollment:&#xD;
&#xD;
          1. Positive urine cotinine test&#xD;
&#xD;
          2. Currently using, or having used within the past month, a nicotine patch&#xD;
&#xD;
          3. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the&#xD;
             Investigator&#xD;
&#xD;
          4. Lack of patency of nares upon physical examination&#xD;
&#xD;
          5. Experienced an exacerbation requiring start of or increase in systemic oral&#xD;
             corticosteroid therapy and/or hospitalization during the last month (ATS COPD&#xD;
             Guidelines 2004)&#xD;
&#xD;
          6. Left ventricular dysfunction as measured by:&#xD;
&#xD;
               1. Screening echocardiographic evidence of left ventricular systolic dysfunction&#xD;
                  (left ventricular ejection fraction (LVEF) &lt; 40%), or&#xD;
&#xD;
               2. Screening echocardiographic evidence of left ventricular diastolic dysfunction &gt;&#xD;
                  moderate (i.e., &gt; Grade 2), or&#xD;
&#xD;
               3. Any history of pulmonary capillary wedge pressure (PCWP), left atrial pressure&#xD;
                  (LAP) or left ventricular end diastolic pressure (LVEDP) &gt; 18 mm Hg as measured&#xD;
                  during cardiac catheterization within the past 6 months unless documented to have&#xD;
                  resolved by a subsequent cardiac catheterization&#xD;
&#xD;
          7. Clinically significant valvular heart disease that may contribute to PH, including&#xD;
             mild or greater aortic valvular disease (aortic stenosis or regurgitation) and/or&#xD;
             moderate or greater mitral valve disease (mitral stenosis or regurgitation), or status&#xD;
             post mitral valve replacement&#xD;
&#xD;
          8. Use within 30 days of screening or current use of approved PH medications such as&#xD;
             sildenafil or bosentan (use of Cialis® or Viagra® for erectile dysfunction is&#xD;
             permitted)&#xD;
&#xD;
          9. Use of investigational drugs or devices within 30 days prior to enrollment into the&#xD;
             study&#xD;
&#xD;
         10. Any underlying medical or psychiatric condition that, in the opinion of the&#xD;
             Investigator, makes the subject an unsuitable candidate for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashika Ahmed, MD</last_name>
    <role>Study Director</role>
    <affiliation>Bellerophon Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jasper Summit Research LLC</name>
      <address>
        <city>Jasper</city>
        <state>Alabama</state>
        <zip>35501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Connection</name>
      <address>
        <city>Flagstaff</city>
        <state>Arizona</state>
        <zip>86001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates P.A.</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radin Cardiovascular Medical Associates</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Connecticut Medical Group PC</name>
      <address>
        <city>Danbury</city>
        <state>Connecticut</state>
        <zip>06810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waterbury Pulmonary Associates</name>
      <address>
        <city>Waterbury</city>
        <state>Connecticut</state>
        <zip>06708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Chest Physicians</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gary J. Richmond, MD, PA</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Coast Institute for Research</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Disease Specialists PA</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <zip>34741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Marcus Research Clinic Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul Medical Research Center Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IMIC, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elite Clinical Research</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Florida Research Phase I-IV</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health &amp; Life Research Solutions Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33173</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research Institute, Inc.</name>
      <address>
        <city>New Port Richey</city>
        <state>Florida</state>
        <zip>34653</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>Research Alliance</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bassette Medical Research Inc.</name>
      <address>
        <city>Sebring</city>
        <state>Florida</state>
        <zip>33872</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Concept Clinical Trials, LLC</name>
      <address>
        <city>Tamarac</city>
        <state>Florida</state>
        <zip>33319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axcess Medical Research</name>
      <address>
        <city>Wellington</city>
        <state>Florida</state>
        <zip>33414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Premier Research Institute</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <zip>32789</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>River Birch Research Alliance LLC</name>
      <address>
        <city>Blue Ridge</city>
        <state>Georgia</state>
        <zip>30513</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Associates of North Georgia</name>
      <address>
        <city>Canton</city>
        <state>Georgia</state>
        <zip>30114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veritas Clinical Specialties, Ltd</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Graves-Gilbert Clinic</name>
      <address>
        <city>Bowling Green</city>
        <state>Kentucky</state>
        <zip>42101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentucky Research Group</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedPharmics LLC</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physician HealthCare Network, PC</name>
      <address>
        <city>Port Huron</city>
        <state>Michigan</state>
        <zip>48060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center-Weiler Division</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Research</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple Lung Center Pulmonary &amp; Critical Care Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lowcountry Lung and Critical Care</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neem Research Group Inc</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gaffney Pharmaceutical Research</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Pharmaceutical Research</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of Rock Hill</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Research</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pioneer Research Solutions, Inc.</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <zip>77479</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond Inc</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zain Research LLC</name>
      <address>
        <city>Richland</city>
        <state>Washington</state>
        <zip>99352</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <disposition_first_submitted>January 30, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>January 30, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">February 18, 2015</disposition_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inhaled nitric oxide (iNO)</keyword>
  <keyword>Pulmonary hypertension (PH)</keyword>
  <keyword>Chronic obstructive pulmonary disease (COPD)</keyword>
  <keyword>Long term oxygen therapy (LTOT)</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>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01728220
org study id: IK-7002-COPD-201
nct id: NCT01728220
lead sponsor: 
has dmc: No
This is a placebo-controlled, double-blind, parallel, randomized, two-part, dose-confirming
      clinical study characterizing the pharmacodynamic effects of pulsed iNO using the combination
      product, inhaled nitric oxide/INOpulse DS-C vs. placebo in subjects with World Health
      Organization (WHO) Group 3 pulmonary hypertension (PH) associated with Chronic Obstructive
      Pulmonary Disease (COPD) on Long Term Oxygen Therapy (LTOT).
This two-part study is designed to confirm the dose of inhaled nitric oxide (NO),
      administered through an investigational pulsed delivery device (INOpulse® DS-C) that results
      in decreased pulmonary arterial systolic pressure (PASP) without significantly affecting
      systemic oxygenation.

      In Part A, 80 subjects will be randomized to 1of 4 treatment groups in a 1:1:1:1 ratio (with
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed
      iNO at a dose of 0.003 mg/kg IBW/hr, 0.010 mg/kg IBW/hr, or 0.015 mg/kg IBW/hr, with a set
      pulse width (PW) of 260 milliseconds (ms). Part A subjects assigned to the placebo group will
      receive nitrogen (N2) at a randomly assigned device setting of 0.003, 0.010 or 0.015 mg/kg
      IBW/hr with a set PW of 260 ms.

      Subjects who were randomized in Part A are permitted to participate in Part B of the study.
      Subjects will need to be re-screened and re-randomized for Part B participation.

      In Part B, 60 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (with
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed
      iNO at either 0.030 mg/kg IBW/hr or 0.075 mg/kg IBW/hr, with a set PW of 260 ms. Part B
      subjects assigned to placebo will receive N2 at a randomly assigned device setting of 0.030
      mg/kg IBW/hr or 0.075 mg/kg IBW/hr with a set PW of 260 ms.

      Part B will use a skewed block randomization scheme with 10 blocks of 6 subjects as follows:

        -  Blocks 1-3: 3 subjects at 0.030 mg/kg IBW/hr, 1 subject at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr

        -  Blocks 4-7: 2 subjects at 0.030 mg/kg IBW/hr, 2 subjects at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr

        -  Blocks 8-10: 1 subject at 0.030 mg/kg IBW/hr, 3 subjects at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO (measured by 2D transthoracic echocardiography with Doppler)
time frame: baseline to end of treatment (1 day)
measure: The secondary outcome is the occurrence of a decrease ≥ 5 mm Hg of partial pressure of oxygen in arterial blood (PaO2) from Baseline after treatment with iNO
time frame: baseline to end of treatment (1 day)
arm group label: Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)
arm group type: Active Comparator
description: Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder delivered via INOpulse® DS-C device
arm group label: Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)
arm group type: Active Comparator
description: Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder delivered via INOpulse® DS-C device
arm group label: Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)
arm group type: Active Comparator
description: Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device
arm group label: Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)
arm group type: Placebo Comparator
description: Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device
arm group label: Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)
arm group type: Active Comparator
description: Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device
arm group label: Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)
arm group type: Active Comparator
description: Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder delivered via INOpulse® DS-C device
arm group label: Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)
arm group type: Active Comparator
description: Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device
intervention type: Combination Product
intervention name: Inhaled NO delivered via INOpulse DS-C Device
description: Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.
arm group label: Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)
arm group label: Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)
arm group label: Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)
arm group label: Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)
arm group label: Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)
intervention type: Combination Product
intervention name: Placebo delivered via INOpulse DS-C Device
description: Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.
arm group label: Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)
arm group label: Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ashika Ahmed, MD
role: Study Director
affiliation: Bellerophon Therapeutics
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country: United States
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