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

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01728220
• Other study ID #: IK-7002-COPD-201
• Status: Completed
• Phase: Phase 2
• Start date: December 2012
• Est. completion date: July 2014

Study information

• Verified date: July 2022
• Source: Bellerophon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Hypertension
• Hypertension, Pulmonary
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Hypertension

Intervention

Combination Product:
• Inhaled NO delivered via INOpulse DS-C Device
Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.
• Placebo delivered via INOpulse DS-C Device
Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.

Locations

Country	Name	City	State
United States	River Birch Research Alliance LLC	Blue Ridge	Georgia
United States	Graves-Gilbert Clinic	Bowling Green	Kentucky
United States	Montefiore Medical Center-Weiler Division	Bronx	New York
United States	Medical Associates of North Georgia	Canton	Georgia
United States	Lowcountry Lung and Critical Care	Charleston	South Carolina
United States	American Health Research	Charlotte	North Carolina
United States	Bay Area Chest Physicians	Clearwater	Florida
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Neem Research Group Inc	Columbia	South Carolina
United States	Western Connecticut Medical Group PC	Danbury	Connecticut
United States	Clinical Trial Connection	Flagstaff	Arizona
United States	Gary J. Richmond, MD, PA	Fort Lauderdale	Florida
United States	Gaffney Pharmaceutical Research	Gaffney	South Carolina
United States	Greenville Pharmaceutical Research	Greenville	South Carolina
United States	East Coast Institute for Research	Jacksonville	Florida
United States	Jasper Summit Research LLC	Jasper	Alabama
United States	Pulmonary Disease Specialists PA	Kissimmee	Florida
United States	Kentucky Research Group	Louisville	Kentucky
United States	MedPharmics LLC	Metairie	Louisiana
United States	Elite Clinical Research	Miami	Florida
United States	Health & Life Research Solutions Inc.	Miami	Florida
United States	IMIC, Inc.	Miami	Florida
United States	San Marcus Research Clinic Inc.	Miami	Florida
United States	South Florida Research Phase I-IV	Miami	Florida
United States	St. Paul Medical Research Center Inc.	Miami	Florida
United States	Advanced Research Institute, Inc.	New Port Richey	Florida
United States	Radin Cardiovascular Medical Associates	Newport Beach	California
United States	Central Florida Pulmonary Group, P.A.	Orlando	Florida
United States	Temple Lung Center Pulmonary & Critical Care Medicine	Philadelphia	Pennsylvania
United States	Pulmonary Associates P.A.	Phoenix	Arizona
United States	Physician HealthCare Network, PC	Port Huron	Michigan
United States	Zain Research LLC	Richland	Washington
United States	Pulmonary Associates of Richmond Inc	Richmond	Virginia
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	Research Alliance	Saint Petersburg	Florida
United States	Bassette Medical Research Inc.	Sebring	Florida
United States	Spartanburg Medical Research	Spartanburg	South Carolina
United States	Pioneer Research Solutions, Inc.	Sugar Land	Texas
United States	Concept Clinical Trials, LLC	Tamarac	Florida
United States	Veritas Clinical Specialties, Ltd	Topeka	Kansas
United States	Waterbury Pulmonary Associates	Waterbury	Connecticut
United States	Axcess Medical Research	Wellington	Florida
United States	Florida Premier Research Institute	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bellerophon Pulse Technologies

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)