Two-Part Dose-Confirming Study of Pulsed Inhaled Nitric Oxide in Subjects With WHO Group 3 Pulmonary Hypertension Associated With COPD

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bellerophon ( Bellerophon Pulse Technologies )
ClinicalTrials.gov Identifier:
NCT01728220
First received: November 13, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Pulmonary Hypertension
Chronic Obstructive Pulmonary Disease
Drug: Inhaled NO
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bellerophon:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: December 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)
Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder
Drug: Inhaled NO
Active Comparator: Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)
Inhaled NO using 3.0 mg/L [2440 ppm] NO minicylinder
Drug: Inhaled NO
Active Comparator: Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)
Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder
Drug: Inhaled NO
Placebo Comparator: Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)
Placebo using 99.999% N2 minicylinder
Other: Placebo
Nitrogen gas
Active Comparator: Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)
Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder
Drug: Inhaled NO
Active Comparator: Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)
Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder
Drug: Inhaled NO
Active Comparator: Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)
Placebo using 99.999% N2 minicylinder
Other: Placebo
Nitrogen gas

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Former smokers with at least 10 pack-years of tobacco cigarette smoking history before study entry and who have stopped smoking ≥ 1 month prior to enrollment
  2. Age ≥ 40 years, ≤ 80 years
  3. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria
  4. A post-bronchodilatory forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.7 and a FEV1 < 60% predicted (values obtained within 6 months prior to screening can be used unless obtained within ± 7 days of an exacerbation; otherwise, the test must be performed during screening)
  5. Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history
  6. Echocardiogram with technical adequacy demonstrating tricuspid regurgitation velocity (TRV) ≥ 2.9 m/s at Screening, as determined by a blinded central echocardiography laboratory
  7. Females of childbearing potential must have a negative pre-treatment urine pregnancy test
  8. Signed informed consent prior to the initiation of any study mandated procedures or assessments

Exclusion criteria:

Subjects who meet any of the following criteria are not eligible for enrollment:

  1. Positive urine cotinine test
  2. Currently using, or having used within the past month, a nicotine patch
  3. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator
  4. Lack of patency of nares upon physical examination
  5. Experienced an exacerbation requiring start of or increase in systemic oral corticosteroid therapy and/or hospitalization during the last month (ATS COPD Guidelines 2004)
  6. Left ventricular dysfunction as measured by:

    1. Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 40%), or
    2. Screening echocardiographic evidence of left ventricular diastolic dysfunction > moderate (i.e., > Grade 2), or
    3. Any history of pulmonary capillary wedge pressure (PCWP), left atrial pressure (LAP) or left ventricular end diastolic pressure (LVEDP) > 18 mm Hg as measured during cardiac catheterization within the past 6 months unless documented to have resolved by a subsequent cardiac catheterization
  7. Clinically significant valvular heart disease that may contribute to PH, including mild or greater aortic valvular disease (aortic stenosis or regurgitation) and/or moderate or greater mitral valve disease (mitral stenosis or regurgitation), or status post mitral valve replacement
  8. Use within 30 days of screening or current use of approved PH medications such as sildenafil or bosentan (use of Cialis® or Viagra® for erectile dysfunction is permitted)
  9. Use of investigational drugs or devices within 30 days prior to enrollment into the study
  10. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01728220

  Hide Study Locations
Locations
United States, Alabama
Jasper Summit Research LLC
Jasper, Alabama, United States, 35501
United States, Arizona
Clinical Trial Connection
Flagstaff, Arizona, United States, 86001
Pulmonary Associates P.A.
Phoenix, Arizona, United States, 85006
United States, California
Radin Cardiovascular Medical Associates
Newport Beach, California, United States, 92663
United States, Connecticut
Western Connecticut Medical Group PC
Danbury, Connecticut, United States, 06810
Waterbury Pulmonary Associates
Waterbury, Connecticut, United States, 06708
United States, Florida
Bay Area Chest Physicians
Clearwater, Florida, United States, 33756
Gary J. Richmond, MD, PA
Fort Lauderdale, Florida, United States, 33316
East Coast Institute for Research
Jacksonville, Florida, United States, 32204
Pulmonary Disease Specialists PA
Kissimmee, Florida, United States, 34741
South Florida Research Phase I-IV
Miami, Florida, United States, 33165
IMIC, Inc.
Miami, Florida, United States, 33140
San Marcus Research Clinic Inc.
Miami, Florida, United States, 33015
Elite Clinical Research
Miami, Florida, United States, 33144
St. Paul Medical Research Center Inc.
Miami, Florida, United States, 33126
Health & Life Research Solutions Inc.
Miami, Florida, United States, 33173
Advanced Research Institute, Inc.
New Port Richey, Florida, United States, 34653
Central Florida Pulmonary Group, P.A.
Orlando, Florida, United States, 32803
Bassette Medical Research Inc.
Sebring, Florida, United States, 33872
Research Alliance
St. Petersburg, Florida, United States, 33710
Concept Clinical Trials, LLC
Tamarac, Florida, United States, 33319
Axcess Medical Research
Wellington, Florida, United States, 33414
Florida Premier Research Institute
Winter Park, Florida, United States, 32789
United States, Georgia
River Birch Research Alliance LLC
Blue Ridge, Georgia, United States, 30513
Medical Associates of North Georgia
Canton, Georgia, United States, 30114
United States, Kansas
Veritas Clinical Specialties, Ltd
Topeka, Kansas, United States, 66606
United States, Kentucky
Graves-Gilbert Clinic
Bowling Green, Kentucky, United States, 42101
Kentucky Research Group
Louisville, Kentucky, United States, 40218
United States, Louisiana
MedPharmics LLC
Metairie, Louisiana, United States, 70006
United States, Michigan
Physician HealthCare Network, PC
Port Huron, Michigan, United States, 48060
United States, New York
Montefiore Medical Center-Weiler Division
Bronx, New York, United States, 10461
United States, North Carolina
American Health Research
Charlotte, North Carolina, United States, 28207
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Temple Lung Center Pulmonary & Critical Care Medicine
Philadelphia, Pennsylvania, United States, 19140
United States, South Carolina
Lowcountry Lung and Critical Care
Charleston, South Carolina, United States, 29406
Neem Research Group Inc
Columbia, South Carolina, United States, 29201
Gaffney Pharmaceutical Research
Gaffney, South Carolina, United States, 29340
Greenville Pharmaceutical Research
Greenville, South Carolina, United States, 29615
Clinical Research of Rock Hill
Rock Hill, South Carolina, United States, 29732
Spartanburg Medical Research
Spartanburg, South Carolina, United States, 29303
United States, Texas
Pioneer Research Solutions, Inc.
Sugar Land, Texas, United States, 77479
United States, Virginia
Pulmonary Associates of Richmond Inc
Richmond, Virginia, United States, 23225
United States, Washington
Zain Research LLC
Richland, Washington, United States, 99352
Sponsors and Collaborators
Bellerophon Pulse Technologies
Investigators
Study Director: Douglas S Greene, PhD Bellerophon Therapeutics
  More Information

No publications provided

Responsible Party: Bellerophon ( Bellerophon Pulse Technologies )
ClinicalTrials.gov Identifier: NCT01728220     History of Changes
Other Study ID Numbers: IK-7002-COPD-201
Study First Received: November 13, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Bellerophon:
Inhaled nitric oxide (iNO)
Pulmonary hypertension (PH)
Chronic obstructive pulmonary disease (COPD)
Long term oxygen therapy (LTOT)

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on September 11, 2014