Clinical Study of Pulsed, Inhaled Nitric Oxide Versus Placebo in Symptomatic Subjects With PAH (INOvation-1)

A Phase 3, Placebo Controlled, Double-Blind, Randomized, Clinical Study to Determine Efficacy, Safety, and Tolerability of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Symptomatic Subjects With PAH (Part 1 and Part 2)

Phase 3, placebo controlled, double-blind, randomized clinical study to determine safety, tolerability, and efficacy of pulsed, inhaled nitric oxide (iNO) versus placebo in symptomatic subjects with pulmonary arterial hypertension (PAH). Part 1 and Part 2

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Inhaled Nitric Oxide 75 mcg/kg IBW/hr; Drug: Placebo

Detailed Description

Phase 3, placebo controlled, double-blind, randomized, clinical study to determine safety, tolerability and efficacy of pulsed inhaled nitric oxide (iNO) versus placebo as add-on therapy in subjects with pulmonary arterial hypertension (PAH) who remain symptomatic on approved PAH monotherapy or combination approved PAH therapy and long term oxygen therapy (LTOT). (Part 1 and Part 2)

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Public Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Sydney, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
• Austria
  • Wien, Austria, 1090
    • AKH-Vienna, Medical University of Vienna
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • Innsbruck Medical University, University Hospital for Internal Medicine VI, Pneumology
• Belgium
  • Bruxelles, Belgium, 1070
    • Hopital Erasme - Service de Cardiologie
  • Brabant
    • Leuven, Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg -
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Faculty of Medicine / Peter Lougheed Center / Respiratory Research
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Lawson Clinical Research Services / London Health Sciences Centre - VH
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital, University Health Network
• Colombia
  • Bogotá D.C.
    • Bogotá, Bogotá D.C., Colombia
      • Fundacion ABOOD Shaio
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
• Czechia
  • Bohemia
    • Praha 2, Bohemia, Czechia, 128 02
      • Vseobecna fakultni nemocnice v Praze (VFN)
• France
  • Montpellier, France, 34295
    • Hôpital Arnaud De Villeneuve - Service des Maladies Respiratoires
  • Nice, France, 06001
    • CHU de Nice Hôpital Pasteur - Pavillon H - Service Pneumologie
  • Normandy
    • Rouen, Normandy, France, 76031
      • Centre Hospitalier Universitaire (CHU) Hopitaux de Rouen - Hopital Charles Nicolle
  • Rhone
    • Grenoble, Rhone, France, 38043
      • Centre Hospitalier Universitaire de Grenoble (CHU Grenoble) - Clinique de Pneumologie
    • St Priest en Jarez, Rhone, France, 42270
      • Centre Hospitalier Universitaire de Saint Etienne
• Germany
  • Berlin, Germany, 12683
    • Unfallkrankenhaus Berlin-Klinik für Innere Medizin/Kardiologie
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • "Universitätsklinikum Freiburg - Medizinische Universitätsklinik
    • Heidelberg, Baden-Württemberg, Germany, 69126
      • Thoraxklinik am Universitätsklinikum Heidelberg-Zentrum für Pulmonale Hypertension
    • Wangen, Baden-Württemberg, Germany, 88239
      • Waldburg-Zeil Kliniken - Fachkliniken Wangen Klinik für Pneumologie
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • Klinikum der Universität Regensburg - Klinik und Poliklinik für Innere Medizin II
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Universitätsmedizin Greifswald Zentrum für innere Medizin Klinik und Poliklinik für Innere Medizin B
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover-Abteilung für Pneumologie
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus - Medizinische Klinik und Poliklinik I
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig-Dept. für Innere MedizinAbteilung für Pneumologie
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
      • Helios Klinikum Erfurt
• Israel
  • Ashqelon, Israel, 7830604
    • Barzilai University Medical Center
  • Beer Sheba, Israel, 84101
    • Soroka Medical Center
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Holon, Israel, 58100
    • The Edith Wolfson Medical Center
  • Jerusalem, Israel
    • Hadassah University Medical Center
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center - Pulmonology Dept.
  • Petaẖ Tiqwa, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center
• Italy
  • BG
    • Bergamo, BG, Italy, 24129
      • Azienda Ospedaliera Papa Giovanni XXIII
  • MI
    • Monza, MI, Italy, 20900
      • Azienda Ospedaliera San Gerardo - Monza
  • PA
    • Palermo, PA, Italy, 90127
      • Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
  • RM
    • Roma, RM, Italy, 00161
      • A.O.U. Policlinico Umberto I- Università La Sapienza
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Vrije Universiteit Medisch Centrum (Vumc)
• Portugal
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte - Hospital de Santa Maria
  • Lisbon
    • Almada, Lisbon, Portugal, 2801-951
      • Hospital Garcia de Orta
  • Mondego
    • Coimbra, Mondego, Portugal, 3049
      • Universidade de Coimbra - Hospitais da Universidade de Coimbra (H.U.C)
• Serbia
  • Belgrade, Serbia, 11080
    • Clinical hospital center Bezanijska Kosa
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia Department of Cardiology and Polyclinic
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Polyclinic, Pulomology Department
  • Belgrade, Serbia, 11070
    • Clinical-Hospital Center Zemun
  • Nis, Serbia, 18000
    • Clinical Center of Nis, Clinic for Cardiovascular Diseases
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Valladolid, Spain, 47003
    • Hospital Universitario de Valladolid
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago de Compostela
  • Canarias
    • Las Palmas de Gran Canaria, Canarias, Spain, 35020
      • Hospital Universitario de Gran Canaria Dr. Negrin
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla (HUMV)
  • Castile - La Mancha
    • Toledo, Castile - La Mancha, Spain, 45004
      • Hospital Virgen de la Salud (HVS)
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Madrid
  • Mallorca
    • Palma de Mallorca, Mallorca, Spain, 7120
      • Hospital Universitario Son Espases
• Ukraine
  • Dnepropetrovsk, Ukraine, 49094
    • Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery of Dnipropetrovsk Regional Council, Department of Cardiology
  • Kharkiv, Ukraine, 61035
    • Municipal Institution of health care "Kharkiv City Clinical Hospital №13", Pulmonology Department №1
  • Kharkiv, Ukraine, 61039
    • Government Institution "L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine", Cardiopulmonology Department
  • Kyiv, Ukraine, 03680
    • National institute of phthisiology and pulmonology
  • Kyiv, Ukraine, 03680
    • National Scientific Centre "M.D. STRAZHESKO INSTITUTE OF CARDIOLOGY, MAS OF UKRAINE"
  • Lviv, Ukraine, 79010
    • Lviv Regional Clinical Hospital, Department of Intesive Care #2
• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom, NW3 3QG
    • Royal Free Hospital
  • Newcastle
    • Newcastle Upon Tyne, Newcastle, United Kingdom, NE7 7DN
      • Freeman Hospital
  • West Dunbartonshire
    • Clydebank, West Dunbartonshire, United Kingdom, G81 4dy
      • Golden Jubilee National Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists, Ltd
    • Tucson, Arizona, United States, 85724-5046
      • University of Arizona Sarver Heart Center
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • La Jolla, California, United States, 92093
      • UC San Diego / Pulmonary, Critical Care and Sleep Medicine Division
    • Los Angeles, California, United States, 90073
      • West Los Angeles VA Healthcare Center
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialists, PA
    • Orlando, Florida, United States, 32803-5727
      • Central Florida Pulmonary Group, PA
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Pulmonary and Critical Care of Atlanta
    • Austell, Georgia, United States, 30106
      • Piedmont Healthcare Pulmonary and Critical Care Research
    • Marietta, Georgia, United States, 30060
      • Wellstar Medical Group - Pulmonary Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Bluhm Cardiovascular Institute, Clinical Trials Unit
    • Peoria, Illinois, United States, 61616
      • HeartCare Midwest
  • Kentucky
    • Louisville, Kentucky, United States, 40202-1332
      • Kentuckiana Pulmonary Associates (KPA), Inc. - Louisville
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5590
      • University of Nebraska Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center - Weiler Division
    • Brooklyn, New York, United States, 11215
      • New York Presbyterian Brooklyn Methodist Hospital - Division of Pulmonary/Critical Care/Sleep
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital, Clinical Trials Center
    • New York, New York, United States, 10279
      • NYU Medical Center, Division Pulmonary, Critical Care and Sleep Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0564
      • University of Cincinnati Medical Ctr, Dept of Internal Medicine / Pulmonary, Critical Care & Sleep Medicine
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43065
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic, PC
    • Portland, Oregon, United States, 97210
      • Legacy Medical Group - Pulmonary Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Singer Research Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29204
      • Medtrial, LLC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Sioux Falls Cardiovascular
  • Texas
    • Dallas, Texas, United States, 75390-8550
      • University of Texas Southwestern Medical Center of Dallas
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Pulmonary Associates of Richmond
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-1615
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent Form (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments
2. A confirmed diagnosis of PAH Group 1 who have either idiopathic PAH (IPAH), heritable PAH, drug and toxin-induced PAH, associated PAH (APAH) with connective tissue disease (CTD), APAH with repaired simple congenital systemic to pulmonary shunt (i.e., atrial septal defect, ventricular septal defect and/or patent ductus arteriosus; complete repair at least 1 year prior to Screening), APAH with human immunodeficiency virus (HIV), or APAH with portal hypertension
3. Subjects receiving at least one PAH specific therapy (ERA or PDE-5 inhibitor, or inhaled, subcutaneous, or intravenous prostacyclin or a prostacyclin analog) with the same type of therapy for at least 3 months with stable dosing 4 weeks prior to Screening. (Subjects should be receiving optimal therapy according to the disease severity)
4. Subjects using oxygen therapy by nasal cannula for at least 4 weeks prior to Screening

5. PAH diagnosis confirmed by RHC within the previous 5 years, according to the following definitions:

   • PVR ≥ 400 dynes.sec.cm-5 (5 Wood units)
   • mPAP ≥ 25 mmHg
   • PCWP or LVEDP ≤ 15 mmHg
   • Subjects who otherwise meet all the inclusion criteria and none of the exclusion criteria but have not undergone a RHC within the previous 5 years may be considered eligible for the study if they undergo a RHC and then meet the pulmonary hemodynamics criterion
6. 6MWD ≥ 100 meters and ≤ 450 meters prior to randomization
7. WHO Functional Class II-IV. Subjects with WHO Functional Class IV should be treated with prostacyclin or a prostacyclin analog (subcutaneous or intravenous), plus at least one additional PAH specific therapy (ERA or PDE-5), if available to the subject and reimbursed by health insurance
8. Age between 18 and 85 years (inclusive)
9. Willingness to use INOpulse delivery device for at least 12 hours per day
10. Willingness to continue on study drug until the subject has completed Week 18 assessments
11. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). All female subjects should take adequate precaution to avoid pregnancy.

Exclusion Criteria:

1. Subjects with known HIV infection who have a history within the past 3 months of any opportunistic pulmonary disease (e.g., tuberculosis, Pneumocystis carinii pneumonia, or other pneumonias) at the time of Screening 2. PAH associated with untreated thyroid disorders, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy 3. Subjects with pulmonary conditions that may contribute to PAH including, but not limited to, chronic bronchiectasis, cystic fibrosis, or other pulmonary condition that the Investigator may deem to contribute to the severity of the disease or impair the delivery of iNO due to airway disease 4. Subjects receiving riociguat 5. Subjects receiving oral prostanoids as monotherapy 7. PAH associated with significant venous or capillary involvement, known or suspected pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis 8. Any subject with WHO PH Groups 2, 3, 4 or 5 9. Subjects with any of the following cardiac abnormalities:

a. Underlying cardiomyopathy or clinically significant aortic or mitral valve disease in the opinion of the investigator b. Left ventricular systolic dysfunction (LVSD), i.e., left ventricular ejection fraction (LVEF) < 40% or left ventricular shortening fraction (LVSF) < 22%, as determined by local reading c. Current symptomatic coronary artery disease, myocardial infarction within 1 year, or any coronary artery interventions within 6 months 10. Systemic hypertension defined as systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg persistent at Screening after a period of rest (treated or untreated) 11. Subjects with a history of deep vein thrombosis, pulmonary embolism/infarction or prothrombotic disorder must have had chronic thromboembolic pulmonary hypertension (CTEPH) excluded by ventilation/perfusion lung (V/Q) scan 12. Severe obstructive lung disease defined as both a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 55% of predicted value 13. Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted; if TLC 60% to 70% predicted, a high resolution CT scan showing diffuse disease or more than mild patchy disease 14. Any subject who develops or has developed a PCWP > 20 mmHg during acute vasodilator testing (AVT) 15. Systemic hypotension defined as SBP < 90 mmHg persistent at Screening after a period of rest 16. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C 17. On dialysis 18. Acute or chronic physical impairment (other than dyspnea due to PAH) that would limit the ability to comply with study procedures or adherence to therapy (i.e., 6MWT), including carrying and wearing the pulsed delivery device per study protocol, or medical problem(s) likely to preclude completion of the study 19. Pregnant or breastfeeding females at Screening 20. Administered L-arginine within 1 month prior to Screening 21. Known concomitant life-threatening disease with a life expectancy less than 1 year 22. Atrial septostomy within 3 months preceding randomization 23. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), Bilevel positive airway presure BiPAP, or any other positive pressure device.

24. Use of investigational drugs or devices within 1 month prior to Screening (other than acute vasodilator testing with iNO) 25. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study 26. Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulse delivery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaled Nitric Oxide 75mcg/KgIBW/Hr; Part 1: 15Mcg/kg IBW/hr during Run-in Period dose titrated to Inhaled Nitric Oxide / 75mcg/KgIBW/Hr upon randomization to treatment arm. Part 2: iNO 75 mcg/kg IBW/hr Open Label Treatment (Open Label Treatment - All Subjects)	Drug: Inhaled Nitric Oxide 75 mcg/kg IBW/hr; Inhaled Nitric Oxide 15mcg/Kg IBW/hr for two week run in period dose titrated to Inhaled Nitric Oxide 75 mcg/kg IBW/hr at randomizationTreatment Period (Week 3 to Week 18); Other Names: iNO; Inhaled Nitric Oxide
Placebo Comparator: Placebo; Part 1: Placebo dose setting 15mcg/kg IBW/hr Run In Period / Placebo dose setting 75 mcg/kg IBW/hr treatment period	Drug: Placebo; Part 1 Placebo arm: Inhaled Nitric Oxide 15mcg/Kg IBW/hrfor two week run in period dose titrated to Inhaled Nitric Oxide 75 mcg/kg IBW/hr at randomizationTreatment Period; Other Names: iNO; Inhaled Nitric Oxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute Walk Distance (6MWD) From Baseline (Randomization) to End of Treatment Period (Week 18)	The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. All patients were required to complete two walks while on chronic oxygen therapy given at a standard rate during the test and throughout the study while using the investigational product (INOpulse device with nitric oxide or matching placebo). The average of two walks at Week 2 visit (2 weeks after Run-In) was used as the Baseline 6MWD.	Change in 6MWD from Week 2 (2 weeks after randomization and run-in period) to Week 18 (end of blinded treatment period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (in Days) to First Clinical Worsening Event (TTCW)	Clinical worsening was assessed continuously from Randomization to Week 18 (End of blinded treatment period). Clinical worsening events were defined as death (all causes), atrial septostomy, hospitalization due to worsening of pulmonary arterial hypertension (PAH), initiation of new pulmonary arterial hypertension treatment including endothelin receptor antagonists [ERAs], phosphodiesterase type-5 [PDE-5] inhibitors or prostanoids, an increase in existing treatment of ERA or PDE-5, increase in the dose or frequency of an inhaled prostanoids, or an increase in the dose of an intravenous or subcutaneous prostanoids by >10%, a decrease of >15% from baseline or >30% compared with the last study related measurement in 6MWD or worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV). All worsening events were entered by the study sites into the eCRF.	From Randomization to Week 18 (End of blinded treatment period)
Number of Participants With an Improvement in World Health Organization Functional Class (WHO FC) Baseline (Randomization) to End of Treatment Period (Week 18)	WHO FC (where Class I is defined as "No limitations in daily physical activities. No symptoms of dyspnea and with routine exertion" and Class IV is defined as "Inability to perform even minimal activities. Signs and symptoms of right heart failure may be present. Dyspnea present at rest") for PAH was taken at randomization (Week 0) for all participants and was assessed after blinded treatment (Week 18). The number of participants that had an improvement (lower functional class) as compared to baseline were measured.	From Randomization to Week 18 (End of blinded treatment period)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma N-Terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Screening to End of Treatment Period (Week 18)	Plasma NT-proBNP concentration is a useful biomarker for the severity of PAH as it is associated with changes in right heart morphology and function. NT-proBNP sample collection occurred at Screening visit (prior to starting study drug at Randomization) and after 16 weeks of blinded treatment therapy (Week 18). The change in NT-proBNP between Screening (28 days prior to baseline/randomization) and the end of blinded treatment period (Week 18) is reported.	From Screening (28 days prior to baseline/randomization) to end of Blinded Treatment Period (Week 18)
Change in Borg Dyspnea Scale Immediately Following 6-minute Walk Test (6MWT) From Baseline (Randomization) to End of Treatment Period (Week 18)	The Borg dyspneas score is a self-rating scale to evaluate the severity of dyspnea (from 0 "no shortness of breath at all" to 10 "very, very severe / maximal") shortness of breath, where high score on the scale signifies a worse score. The self assessment was collected from each participant immediately after each 6-minute walk test throughout the blinded treatment period. The change in Borg dyspnea Score at the end of the blinded treatment period (Week 18) compared to baseline (randomization) (Week 0) is reported.	From Randomization to Week 18 (End of blinded treatment period)
Number of Participants With an Unsatisfactory Clinical Response From Baseline (Randomization) to End of Treatment Period (Week 18)	Unsatisfactory Clinical Response was defined as the number of participants with WHO Functional Class III (defined as moderate dyspnea with routine activities and activities of daily living. No symptoms at rest.) or Class IV (defined as inability to perform even minimal activities. Signs and symptoms of right heart failure may be present. Dyspnea present at rest) with no improvement in 6-minute walk distance (6MWD) from baseline to end of blinded treatment period (Week 18).	From Randomization to Week 18 (End of blinded treatment period)

Collaborators and Investigators

• Sponsor: Bellerophon Pulse Technologies
• Collaborators: Worldwide Clinical Trials
• Investigators: Study Director: Ashika Ahmed, MD, Bellerophon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: January 19, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; PAH; Inhaled Nitric Oxide; iNO; oxygen therapy; long term oxygen therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: PULSE-PAH-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO