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

This study is currently recruiting participants.
Verified February 2014 by INO Therapeutics
Sponsor:
Information provided by (Responsible Party):
INO Therapeutics
ClinicalTrials.gov Identifier:
NCT01728220
First received: November 13, 2012
Last updated: February 10, 2014
Last verified: February 2014

November 13, 2012
February 10, 2014
December 2012
April 2014   (final data collection date for primary outcome 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) ] [ Designated as safety issue: No ]
Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO [ Time Frame: baseline to end of treatment (1 day) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01728220 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Two-Part Dose-Confirming Study of Pulsed Inhaled Nitric Oxide in Subjects With WHO Group 3 Pulmonary Hypertension Associated With COPD
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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Pulmonary Hypertension
  • Chronic Obstructive Pulmonary Disease
  • Drug: Inhaled NO
  • Other: Placebo
    Nitrogen gas
  • 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: Other: Placebo
  • Active Comparator: Inhaled NO @ 0.030 mg/kg IBW/hr (Part B)
    Inhaled NO using 6.0 mg/L [4880 ppm] NO minicylinder
    Intervention: 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
    Intervention: Drug: Inhaled NO
  • Active Comparator: Placebo random @ 0.030 or 0.075 mg/kg/IBW (Part B)
    Placebo using 99.999% N2 minicylinder
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
140
June 2014
April 2014   (final data collection date for primary outcome measure)

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
Both
40 Years to 80 Years
No
Contact: Carmen Arencibia 908-238-6741 carmen.arencibia@ikaria.com
United States
 
NCT01728220
IK-7002-COPD-201
No
INO Therapeutics
INO Therapeutics
Not Provided
Study Director: Douglas S Greene, PhD Bellerophon
INO Therapeutics
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP