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

NCT01728220 | Completed Phase 2

• 1 other identifier: IK-7002-COPD-201
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 43

Brief Summary

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).

Conditions

Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease

Keywords

Inhaled nitric oxide (iNO); Pulmonary hypertension (PH); Chronic obstructive pulmonary disease (COPD); Long term oxygen therapy (LTOT)

Outcome Measures

Primary Outcomes (1)

• Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO (measured by 2D transthoracic echocardiography with Doppler)

  baseline to end of treatment (1 day)

Secondary Outcomes (1)

• 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

  baseline to end of treatment (1 day)

Study Arms (7)

Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A)

ACTIVE COMPARATOR

Inhaled NO using 3.0 mg/L \[2440 ppm\] NO minicylinder delivered via INOpulse® DS-C device

Combination Product: Inhaled NO delivered via INOpulse DS-C Device

Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A)

ACTIVE COMPARATOR

Inhaled NO using 3.0 mg/L \[2440 ppm\] NO minicylinder delivered via INOpulse® DS-C device

Combination Product: Inhaled NO delivered via INOpulse DS-C Device

Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A)

ACTIVE COMPARATOR

Inhaled NO using 6.0 mg/L \[4880 ppm\] NO minicylinder delivered via INOpulse® DS-C device

Combination Product: Inhaled NO delivered via INOpulse DS-C Device

Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A)

PLACEBO COMPARATOR

Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device

Combination Product: Placebo delivered via INOpulse DS-C Device

Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)

ACTIVE COMPARATOR

Inhaled NO using 6.0 mg/L \[4880 ppm\] NO minicylinder delivered via INOpulse® DS-C device

Combination Product: Inhaled NO delivered via INOpulse DS-C Device

Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)

ACTIVE COMPARATOR

Inhaled NO using 6.0 mg/L \[4880 ppm\] NO minicylinder delivered via INOpulse® DS-C device

Combination Product: Inhaled NO delivered via INOpulse DS-C Device

Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)

ACTIVE COMPARATOR

Placebo using 99.999% N2 minicylinder delivered via INOpulse® DS-C device

Combination Product: Placebo delivered via INOpulse DS-C Device

Interventions

Inhaled NO delivered via INOpulse DS-C Device COMBINATION_PRODUCT

Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.

Inhaled NO @ 0.003 mg/kg/ ideal body weight (IBW)/hr (Part A); Inhaled NO @ 0.010 mg/kg/IBW/hr (Part A); Inhaled NO @ 0.015 mg/kg/IBW/hr (Part A); Inhaled NO @ 0.030 mg/kg IBW/hr (Part B); Inhaled NO @ 0.075 mg/kg IBW/hr (Part B)

Placebo delivered via INOpulse DS-C Device COMBINATION_PRODUCT

Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.

Placebo random @ 0.003, 0.010 or 0.015 mg/kg/IBW/hr (Part A); Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥ 40 years, ≤ 80 years
• A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria
• 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)
• Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history
• Echocardiogram with technical adequacy demonstrating tricuspid regurgitation velocity (TRV) ≥ 2.9 m/s at Screening, as determined by a blinded central echocardiography laboratory
• Females of childbearing potential must have a negative pre-treatment urine pregnancy test
• Signed informed consent prior to the initiation of any study mandated procedures or assessments

You may not qualify if:

• Subjects who meet any of the following criteria are not eligible for enrollment:
• Positive urine cotinine test
• Currently using, or having used within the past month, a nicotine patch
• A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator
• Lack of patency of nares upon physical examination
• Experienced an exacerbation requiring start of or increase in systemic oral corticosteroid therapy and/or hospitalization during the last month (ATS COPD Guidelines 2004)
• Left ventricular dysfunction as measured by:
• Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) \< 40%), or
• Screening echocardiographic evidence of left ventricular diastolic dysfunction \> moderate (i.e., \> Grade 2), or
• 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
• 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
• 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)
• Use of investigational drugs or devices within 30 days prior to enrollment into the study
• Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study

Sponsors & Collaborators

• Bellerophon Pulse Technologies: lead

Study Sites (43)

Jasper Summit Research LLC

Jasper, Alabama, 35501, United States

Location

Clinical Trial Connection

Flagstaff, Arizona, 86001, United States

Location

Pulmonary Associates P.A.

Phoenix, Arizona, 85006, United States

Location

Radin Cardiovascular Medical Associates

Newport Beach, California, 92663, United States

Location

Western Connecticut Medical Group PC

Danbury, Connecticut, 06810, United States

Location

Waterbury Pulmonary Associates

Waterbury, Connecticut, 06708, United States

Location

Bay Area Chest Physicians

Clearwater, Florida, 33756, United States

Location

Gary J. Richmond, MD, PA

Fort Lauderdale, Florida, 33316, United States

Location

East Coast Institute for Research

Jacksonville, Florida, 32204, United States

Location

Pulmonary Disease Specialists PA

Kissimmee, Florida, 34741, United States

Location

San Marcus Research Clinic Inc.

Miami, Florida, 33015, United States

Location

St. Paul Medical Research Center Inc.

Miami, Florida, 33126, United States

Location

IMIC, Inc.

Miami, Florida, 33140, United States

Location

Elite Clinical Research

Miami, Florida, 33144, United States

Location

South Florida Research Phase I-IV

Miami, Florida, 33165, United States

Location

Health & Life Research Solutions Inc.

Miami, Florida, 33173, United States

Location

Advanced Research Institute, Inc.

New Port Richey, Florida, 34653, United States

Location

Central Florida Pulmonary Group, P.A.

Orlando, Florida, 32803, United States

Location

Bassette Medical Research Inc.

Sebring, Florida, 33872, United States

Location

Research Alliance

St. Petersburg, Florida, 33710, United States

Location

Concept Clinical Trials, LLC

Tamarac, Florida, 33319, United States

Location

Axcess Medical Research

Wellington, Florida, 33414, United States

Location

Florida Premier Research Institute

Winter Park, Florida, 32789, United States

Location

River Birch Research Alliance LLC

Blue Ridge, Georgia, 30513, United States

Location

Medical Associates of North Georgia

Canton, Georgia, 30114, United States

Location

Veritas Clinical Specialties, Ltd

Topeka, Kansas, 66606, United States

Location

Graves-Gilbert Clinic

Bowling Green, Kentucky, 42101, United States

Location

Kentucky Research Group

Louisville, Kentucky, 40218, United States

Location

MedPharmics LLC

Metairie, Louisiana, 70006, United States

Location

Physician HealthCare Network, PC

Port Huron, Michigan, 48060, United States

Location

Montefiore Medical Center-Weiler Division

The Bronx, New York, 10461, United States

Location

American Health Research

Charlotte, North Carolina, 28207, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Temple Lung Center Pulmonary & Critical Care Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Lowcountry Lung and Critical Care

Charleston, South Carolina, 29406, United States

Location

Neem Research Group Inc

Columbia, South Carolina, 29201, United States

Location

Gaffney Pharmaceutical Research

Gaffney, South Carolina, 29340, United States

Location

Greenville Pharmaceutical Research

Greenville, South Carolina, 29615, United States

Location

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

Spartanburg Medical Research

Spartanburg, South Carolina, 29303, United States

Location

Pioneer Research Solutions, Inc.

Sugar Land, Texas, 77479, United States

Location

Pulmonary Associates of Richmond Inc

Richmond, Virginia, 23225, United States

Location

Zain Research LLC

Richland, Washington, 99352, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ashika Ahmed, MD

  Bellerophon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 19, 2012
• Study Start: December 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 27, 2023

Record last verified: 2022-07

Locations

US (43)