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

Tracking Information
First Submitted Date ICMJE	November 13, 2012
First Posted Date ICMJE	November 19, 2012
Last Update Posted Date	February 18, 2015
Study Start Date ICMJE	December 2012
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 5, 2013)	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) ]
Original Primary Outcome Measures ICMJE; (submitted: November 13, 2012)	Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO [ Time Frame: baseline to end of treatment (1 day) ]
Change History	Complete list of historical versions of study NCT01728220 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 13, 2012)	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) ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Two-Part Dose-Confirming Study of Pulsed Inhaled Nitric Oxide in Subjects With WHO Group 3 Pulmonary Hypertension Associated With COPD
Official Title ICMJE	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
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).
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
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease
Intervention ICMJE	Drug: Inhaled NO; Other: Placebo Nitrogen gas
Study Arms	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
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 23, 2014)	159
Original Estimated Enrollment ICMJE; (submitted: November 13, 2012)	80
Actual Study Completion Date	July 2014
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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 Exclusion criteria: 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
Sex/Gender	Sexes Eligible for Study: All
Ages	40 Years to 80 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01728220
Other Study ID Numbers ICMJE	IK-7002-COPD-201
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Bellerophon ( Bellerophon Pulse Technologies )
Study Sponsor ICMJE	Bellerophon Pulse Technologies
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Douglas S Greene, PhD Bellerophon Therapeutics
PRS Account	Bellerophon
Verification Date	January 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP