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



Status:Completed
Conditions:Chronic Obstructive Pulmonary Disease, High Blood Pressure (Hypertension), Pulmonary
Therapuetic Areas:Cardiology / Vascular Diseases, Pulmonary / Respiratory Diseases
Healthy:No
Age Range:40 - 80
Updated:7/13/2018
Start Date:December 2012
End Date:July 2014

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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

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

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
We found this trial at
43
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616 E Street
Clearwater, Florida 33756
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11701 San Jose Blvd # 32
Jacksonville, Florida 32223
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3800 Houma Blvd., Suite 335
Metairie, Louisiana 70006
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326 North Mills Avenue
Orlando, Florida 32803
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485 Simuel Road.
Spartanburg, South Carolina 29303
(864) 583-1556
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Blue Ridge, Georgia 30513
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Bowling Green, Kentucky 42101
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Canton, Georgia 30114
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Charleston, South Carolina 29406
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Charlotte, North Carolina 28207
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Columbia, South Carolina 29201
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Danbury, Connecticut 06810
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Flagstaff, Arizona 86001
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Fort Lauderdale, Florida 33316
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Gaffney, South Carolina 29340
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Greenville, South Carolina 29615
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Jasper, Alabama 35501
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Kissimmee, Florida 34741
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Louisville, Kentucky 40217
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Miami, Florida 33015
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Miami, Florida 33140
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Miami, Florida 33144
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New Port Richey, Florida
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Newport Beach, California 92663
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Phoenix, Arizona 85006
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Port Huron, Michigan 48060
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Richland, Washington 99352
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Richmond, Virginia 23225
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Rock Hill, South Carolina 29732
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Saint Petersburg, Florida 33710
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Sebring, Florida 33872
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Sugar Land, Texas 77479
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Tamarac, Florida 33319
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Topeka, Kansas 66606
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Waterbury, Connecticut
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Wellington, Florida 33414
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Winter Park, Florida 32789
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