search
Back to results

A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AIR001 (sodium nitrite inhalation solution)
Sponsored by
Aires Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring AIR001, sodium nitrite, PAH, Pulmonary Arterial Hypertension, inhaled sodium nitrite

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed and dated informed consent document
  2. Able to comply with study procedures
  3. Diagnosis of PAH as classified by:

    1. Idiopathic (IPAH) or heritable(HPAH); or
    2. PAH associated with CTD; Systemic Sclerosis, Limited Scleroderma, Mixed, SLE, or overlap syndrome;
    3. PAH associated with HIV ii. Simple, congenital shunts at least one year post repair. iii. Exposure to legal drugs, chemicals and toxins
  4. Cardiac catheterization prior to Screening with:

    1. mPAP ≥ 25 mmHg (at rest);
    2. PCWP ≤ 15 mmHg; and
    3. PVR > 3 mmHg/L/min or 240 dyn.sec/cm5
  5. A qualification cardiac catheterization, to confirm the persistence and severity of PAH, if the diagnostic catheterization was performed more than 30 days prior to Baseline

    1. Confirms diagnosis;
    2. PVR above 300 dyn.sec/cm5 to demonstrate the persistence and severity of PAH; and
    3. No change in disease-specific PAH therapy since the qualification catheterization used
  6. Newly diagnosed PAH on no disease-specific PAH therapy or previously diagnosed on oral disease-specific PAH therapy for 90 days prior with either an ETRA and/or PDE-5i
  7. Has PFTs within 180 days prior to Baseline with no evidence of significant parenchymal lung disease defined as:

    • FEV1 ≤ 70% (predicted) (pre-bronchodilators);
    • FEV1/FVC ≤ 70% (pre-bronchodilators); or
    • Total lung capacity < 70% (predicted).
  8. Has WHO/NYHA FC II- IV.
  9. ≥ 18 and ≤ 75 years.
  10. Weight ≥ 40 kg.
  11. Has 6MWT distance at least 50 meters.
  12. Had a V/Q scan or pulmonary angiogram prior to Screening that shows no evidence of thromboembolic disease
  13. If on the following: vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine; must be on a stable dose 30 days prior to Baseline and maintained throughout the study
  14. If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 30 days
  15. Women of childbearing potential must be using at least one form of medically acceptable contraception. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception

Exclusion Criteria:

  1. Participation in a device or other interventional clinical studies, within 30 days of Baseline and during study participation
  2. Participation in a cardio-pulmonary rehabilitation program based upon exercise within 30 days prior to Baseline and/or during the study
  3. Has uncontrolled systemic hypertension: SBP > 160 millimeter of mercury (mmHg) or DBP > 100 mmHg during Screening
  4. SBP < 90 mmHg at Screening or Baseline
  5. History of orthostatic hypotension or at the time of Screening; defined as a drop in SBP by ≥ 20 mmHg or DBP of ≥ 10 mmHg during Screening
  6. History of left-sided heart disease and/or clinically significant cardiac disease, including:

    1. Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild;
    2. Pericardial constriction;
    3. Restrictive or congestive cardiomyopathy;
    4. Left ventricular ejection fraction < 40%
    5. Left ventricular shortening fraction < 22% by ECHO prior to Screening;
    6. Symptomatic coronary disease
  7. Significant (2+ for regurgitation) valvular disease other than TR or PR
  8. Acutely decompensated heart failure within 30 days prior to Baseline
  9. History of atrial septostomy within 180 days prior to Baseline
  10. History of obstructive sleep apnea (treated, untreated or resolved)
  11. Diagnosis of Down syndrome
  12. Moderate to severe hepatic impairment
  13. Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an eGFR < 30 mL/min at Screening, or requires dialysis
  14. Has a Hgb concentration < 8.5 g/dL at Screening
  15. Personal or family history of the following:

    1. Congenital or acquired methemoglobinemia;
    2. RBC CYPB5 reductase deficiency
  16. G6PD deficiency or any contraindication to receiving methylene blue
  17. For subjects with HIV any of the following:

    • Concomitant active opportunistic infections 180 days prior to Screening;
    • Detectable viral load within 90 days of Screening;
    • T-cell count < 200 mm3 within 90 days of Screening;
    • Changes in antiretroviral regimen within 90 days of Screening;
    • Using inhaled pentamidine
  18. Receiving chronic treatment with prostacyclin/prostacyclin analogue within 60 days of Baseline
  19. Requirement of intravenous inotropes within 30 days prior to Baseline
  20. The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 30 days prior to Baseline and until EOS or Termination
  21. Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate
  22. History of malignancy within 5-years prior to Baseline
  23. Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
  24. Has a disorder that compromises the ability to give informed consent
  25. Is currently pregnant or breastfeeding or intends to become pregnant
  26. Investigators, study staff or their immediate families

Sites / Locations

  • UCSD Medical Center
  • UCLA Medical Center
  • University of Colorado Denver
  • Kentuckiana Pulmonary Associates
  • University of Maryland Medical Center
  • Tufts Medical Center
  • Brigham and Women's Hospital
  • Boston University School of Medicine
  • Washington University School of Medicine
  • Duke University Medical Center
  • University of Cincinnati
  • The Ohio State University Medical Center
  • University of Pittsburgh Medical Center
  • University of Texas Southwestern Medical Center
  • Baylor College of Medicine
  • Inova Fairfax Hospital
  • Aurora St. Luke's Medical Center
  • St. Vincent's Hospital
  • The Prince Charles Hospital
  • Royal Hobart Hospital
  • The Alfred Hospital
  • Gottsegen Gyorgy Hungarian
  • Semmelweis Karlocai
  • University of Debrecen
  • University of Szeged

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

80mg AIR001 four times daily

46mg AIR001 four times daily

80mg AIR001 once daily

Arm Description

80mg AIR001 nebulized four times daily for 16 weeks

46mg AIR001 nebulized four times daily for 16 weeks

80mg AIR001 nebulized once daily for 16 weeks

Outcomes

Primary Outcome Measures

Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).

Secondary Outcome Measures

Time to Clinical Worsening (TTCW), other hemodynamics, and safety
To evaluate the effect of inhaled nebulized AIR001 administered according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with WHO Group 1 PAH for 16 weeks, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and change from Baseline to Week 16 in the following: Pulmonary Vascular Resistance Index (PVRI), N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), 6-Minute Walk Distance (6MWD) assessed at peak, 6MWD assessed prior to AIR001 nebulization (trough), Cardiac Output (CO), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), WHO/NYHA Functional Class (FC), Quality of Life (QOL) as measured by Short-Form 36 (SF-36), Borg Dyspnea Index, Mean pulmonary artery pressure (mPAP), PVR measured at trough, PVR/systemic vascular resistance (SVR) ratio at trough and peak, To evaluate the safety and tolerability of AIR001 in subjects with WHO Group 1 PAH.

Full Information

First Posted
November 8, 2012
Last Updated
April 7, 2014
Sponsor
Aires Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01725256
Brief Title
A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)
Official Title
A Phase 2, Multi-Center, Open-label, Randomized, Parallel-Dose Study to Determine the Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
Terminated early dt to acquisition of Sponsor and change in corporate priorities
Study Start Date
November 2012 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aires Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of an investigational/experimental drug called AIR001. To test the effectiveness, the study will evaluate how AIR001 affects the blood vessels in the lungs and the function of the heart. This will be done by monitoring changes in Pulmonary Vascular Resistance (PVR); from Baseline/Day 1 (start of study drug) to Week 16 of the study. PVR measures the resistance to flow in the blood vessels of the lungs. The study will include other assessments to evaluate the effect of the study drug on PAH, including measurements of exercise ability and evaluations of PAH disease symptoms.
Detailed Description
The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
AIR001, sodium nitrite, PAH, Pulmonary Arterial Hypertension, inhaled sodium nitrite

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
80mg AIR001 four times daily
Arm Type
Experimental
Arm Description
80mg AIR001 nebulized four times daily for 16 weeks
Arm Title
46mg AIR001 four times daily
Arm Type
Experimental
Arm Description
46mg AIR001 nebulized four times daily for 16 weeks
Arm Title
80mg AIR001 once daily
Arm Type
Experimental
Arm Description
80mg AIR001 nebulized once daily for 16 weeks
Intervention Type
Drug
Intervention Name(s)
AIR001 (sodium nitrite inhalation solution)
Other Intervention Name(s)
sodium nitrite inhalation solution, sodium nitrite, nitrite
Intervention Description
Dose arms specify dose loaded into the I-neb AAD System nebulizer
Primary Outcome Measure Information:
Title
Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
Description
The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Time to Clinical Worsening (TTCW), other hemodynamics, and safety
Description
To evaluate the effect of inhaled nebulized AIR001 administered according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with WHO Group 1 PAH for 16 weeks, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and change from Baseline to Week 16 in the following: Pulmonary Vascular Resistance Index (PVRI), N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), 6-Minute Walk Distance (6MWD) assessed at peak, 6MWD assessed prior to AIR001 nebulization (trough), Cardiac Output (CO), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), WHO/NYHA Functional Class (FC), Quality of Life (QOL) as measured by Short-Form 36 (SF-36), Borg Dyspnea Index, Mean pulmonary artery pressure (mPAP), PVR measured at trough, PVR/systemic vascular resistance (SVR) ratio at trough and peak, To evaluate the safety and tolerability of AIR001 in subjects with WHO Group 1 PAH.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed and dated informed consent document Able to comply with study procedures Diagnosis of PAH as classified by: Idiopathic (IPAH) or heritable(HPAH); or PAH associated with CTD; Systemic Sclerosis, Limited Scleroderma, Mixed, SLE, or overlap syndrome; PAH associated with HIV ii. Simple, congenital shunts at least one year post repair. iii. Exposure to legal drugs, chemicals and toxins Cardiac catheterization prior to Screening with: mPAP ≥ 25 mmHg (at rest); PCWP ≤ 15 mmHg; and PVR > 3 mmHg/L/min or 240 dyn.sec/cm5 A qualification cardiac catheterization, to confirm the persistence and severity of PAH, if the diagnostic catheterization was performed more than 30 days prior to Baseline Confirms diagnosis; PVR above 300 dyn.sec/cm5 to demonstrate the persistence and severity of PAH; and No change in disease-specific PAH therapy since the qualification catheterization used Newly diagnosed PAH on no disease-specific PAH therapy or previously diagnosed on oral disease-specific PAH therapy for 90 days prior with either an ETRA and/or PDE-5i Has PFTs within 180 days prior to Baseline with no evidence of significant parenchymal lung disease defined as: FEV1 ≤ 70% (predicted) (pre-bronchodilators); FEV1/FVC ≤ 70% (pre-bronchodilators); or Total lung capacity < 70% (predicted). Has WHO/NYHA FC II- IV. ≥ 18 and ≤ 75 years. Weight ≥ 40 kg. Has 6MWT distance at least 50 meters. Had a V/Q scan or pulmonary angiogram prior to Screening that shows no evidence of thromboembolic disease If on the following: vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine; must be on a stable dose 30 days prior to Baseline and maintained throughout the study If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 30 days Women of childbearing potential must be using at least one form of medically acceptable contraception. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception Exclusion Criteria: Participation in a device or other interventional clinical studies, within 30 days of Baseline and during study participation Participation in a cardio-pulmonary rehabilitation program based upon exercise within 30 days prior to Baseline and/or during the study Has uncontrolled systemic hypertension: SBP > 160 millimeter of mercury (mmHg) or DBP > 100 mmHg during Screening SBP < 90 mmHg at Screening or Baseline History of orthostatic hypotension or at the time of Screening; defined as a drop in SBP by ≥ 20 mmHg or DBP of ≥ 10 mmHg during Screening History of left-sided heart disease and/or clinically significant cardiac disease, including: Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild; Pericardial constriction; Restrictive or congestive cardiomyopathy; Left ventricular ejection fraction < 40% Left ventricular shortening fraction < 22% by ECHO prior to Screening; Symptomatic coronary disease Significant (2+ for regurgitation) valvular disease other than TR or PR Acutely decompensated heart failure within 30 days prior to Baseline History of atrial septostomy within 180 days prior to Baseline History of obstructive sleep apnea (treated, untreated or resolved) Diagnosis of Down syndrome Moderate to severe hepatic impairment Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an eGFR < 30 mL/min at Screening, or requires dialysis Has a Hgb concentration < 8.5 g/dL at Screening Personal or family history of the following: Congenital or acquired methemoglobinemia; RBC CYPB5 reductase deficiency G6PD deficiency or any contraindication to receiving methylene blue For subjects with HIV any of the following: Concomitant active opportunistic infections 180 days prior to Screening; Detectable viral load within 90 days of Screening; T-cell count < 200 mm3 within 90 days of Screening; Changes in antiretroviral regimen within 90 days of Screening; Using inhaled pentamidine Receiving chronic treatment with prostacyclin/prostacyclin analogue within 60 days of Baseline Requirement of intravenous inotropes within 30 days prior to Baseline The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 30 days prior to Baseline and until EOS or Termination Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate History of malignancy within 5-years prior to Baseline Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation Has a disorder that compromises the ability to give informed consent Is currently pregnant or breastfeeding or intends to become pregnant Investigators, study staff or their immediate families
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adaani E Frost, M.D.
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSD Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Kentuckiana Pulmonary Associates
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110-1093
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Aurora St. Luke's Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
St. Vincent's Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Gottsegen Gyorgy Hungarian
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Semmelweis Karlocai
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
University of Debrecen
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
University of Szeged
City
Szeged
ZIP/Postal Code
6720
Country
Hungary

12. IPD Sharing Statement

Citations:
PubMed Identifier
17544026
Citation
Ahanchi SS, Tsihlis ND, Kibbe MR. The role of nitric oxide in the pathophysiology of intimal hyperplasia. J Vasc Surg. 2007 Jun;45 Suppl A:A64-73. doi: 10.1016/j.jvs.2007.02.027.
Results Reference
background
PubMed Identifier
21436585
Citation
Alef MJ, Vallabhaneni R, Carchman E, Morris SM Jr, Shiva S, Wang Y, Kelley EE, Tarpey MM, Gladwin MT, Tzeng E, Zuckerbraun BS. Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. J Clin Invest. 2011 Apr;121(4):1646-56. doi: 10.1172/JCI44079. Epub 2011 Mar 23.
Results Reference
background
PubMed Identifier
12091180
Citation
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. Erratum In: Am J Respir Crit Care Med. 2016 May 15;193(10):1185.
Results Reference
background
PubMed Identifier
19555859
Citation
Badesch DB, Champion HC, Gomez Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S55-S66. doi: 10.1016/j.jacc.2009.04.011.
Results Reference
background
PubMed Identifier
19661447
Citation
Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6.
Results Reference
background
PubMed Identifier
21225278
Citation
Barbosa PB, Ferreira EM, Arakaki JS, Takara LS, Moura J, Nascimento RB, Nery LE, Neder JA. Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension. Eur J Appl Physiol. 2011 Aug;111(8):1851-61. doi: 10.1007/s00421-010-1799-6. Epub 2011 Jan 12.
Results Reference
background
PubMed Identifier
16740981
Citation
Battistini B, Berthiaume N, Kelland NF, Webb DJ, Kohan DE. Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug. Exp Biol Med (Maywood). 2006 Jun;231(6):653-95.
Results Reference
background
PubMed Identifier
8989070
Citation
Battle RW, Davitt MA, Cooper SM, Buckley LM, Leib ES, Beglin PA, Tischler MD. Prevalence of pulmonary hypertension in limited and diffuse scleroderma. Chest. 1996 Dec;110(6):1515-9. doi: 10.1378/chest.110.6.1515.
Results Reference
background
PubMed Identifier
25696328
Citation
Bergstra A, van den Heuvel AF, Zijlstra F, Berger RM, Mook GA, van Veldhuisen DJ. Validation of Fick cardiac output calculated with assumed oxygen consumption: a study of cardiac output during epoprostenol. Neth Heart J. 2004 May;12(5):208-213.
Results Reference
background
PubMed Identifier
17010807
Citation
Channick RN, Olschewski H, Seeger W, Staub T, Voswinckel R, Rubin LJ. Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J Am Coll Cardiol. 2006 Oct 3;48(7):1433-7. doi: 10.1016/j.jacc.2006.05.070. Epub 2006 Sep 14.
Results Reference
background
PubMed Identifier
15831842
Citation
Chaouat A, Bugnet AS, Kadaoui N, Schott R, Enache I, Ducolone A, Ehrhart M, Kessler R, Weitzenblum E. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Jul 15;172(2):189-94. doi: 10.1164/rccm.200401-006OC. Epub 2005 Apr 14.
Results Reference
background
PubMed Identifier
8035319
Citation
Clozel M, Breu V, Gray GA, Kalina B, Loffler BM, Burri K, Cassal JM, Hirth G, Muller M, Neidhart W, et al. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther. 1994 Jul;270(1):228-35.
Results Reference
background
PubMed Identifier
14595407
Citation
Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003 Dec;9(12):1498-505. doi: 10.1038/nm954. Epub 2003 Nov 2.
Results Reference
background
PubMed Identifier
17893272
Citation
Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007 Oct 16;116(16):1821-31. doi: 10.1161/CIRCULATIONAHA.107.712133. Epub 2007 Sep 24.
Results Reference
background
PubMed Identifier
15483284
Citation
Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004 Oct 14;351(16):1655-65. doi: 10.1056/NEJMra035488. No abstract available.
Results Reference
background
PubMed Identifier
19749199
Citation
Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT); Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009 Dec;34(6):1219-63. doi: 10.1183/09031936.00139009. Epub 2009 Sep 12. No abstract available.
Results Reference
background
PubMed Identifier
19555854
Citation
Ghofrani HA, Barst RJ, Benza RL, Champion HC, Fagan KA, Grimminger F, Humbert M, Simonneau G, Stewart DJ, Ventura C, Rubin LJ. Future perspectives for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S108-S117. doi: 10.1016/j.jacc.2009.04.014.
Results Reference
background
PubMed Identifier
7540722
Citation
Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 1995 Jul 27;333(4):214-21. doi: 10.1056/NEJM199507273330403.
Results Reference
background
PubMed Identifier
21172428
Citation
Gielis JF, Lin JY, Wingler K, Van Schil PE, Schmidt HH, Moens AL. Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med. 2011 Apr 1;50(7):765-76. doi: 10.1016/j.freeradbiomed.2010.12.018. Epub 2010 Dec 21.
Results Reference
background
PubMed Identifier
16798825
Citation
Gladwin MT, Raat NJ, Shiva S, Dezfulian C, Hogg N, Kim-Shapiro DB, Patel RP. Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2026-35. doi: 10.1152/ajpheart.00407.2006. Epub 2006 Jun 23.
Results Reference
background
PubMed Identifier
19020327
Citation
Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008 Nov 20;359(21):2254-65. doi: 10.1056/NEJMra0804411. No abstract available.
Results Reference
background
PubMed Identifier
19555853
Citation
Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JX, Humbert M. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S10-S19. doi: 10.1016/j.jacc.2009.04.006.
Results Reference
background
Citation
Hassoun PM. Pulmonary arterial hypertension complicating connective tissue disease. In: Humbert, M, Lynch JP, Eds. Pulmonary Hypertension. New York: Informa Healthcare USA, Inc. 2010: 161-175
Results Reference
background
PubMed Identifier
15194174
Citation
Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):13S-24S. doi: 10.1016/j.jacc.2004.02.029.
Results Reference
background
PubMed Identifier
15459304
Citation
Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. No abstract available.
Results Reference
background
PubMed Identifier
15361865
Citation
Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG, Gladwin MT. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004 Oct;10(10):1122-7. doi: 10.1038/nm1109. Epub 2004 Sep 12.
Results Reference
background
PubMed Identifier
7658874
Citation
Kiowski W, Sutsch G, Hunziker P, Muller P, Kim J, Oechslin E, Schmitt R, Jones R, Bertel O. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet. 1995 Sep 16;346(8977):732-6. doi: 10.1016/s0140-6736(95)91504-4.
Results Reference
background
PubMed Identifier
17133488
Citation
Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: Results from a 10-year screening algorithm. Hepatology. 2006 Dec;44(6):1502-10. doi: 10.1002/hep.21431.
Results Reference
background
PubMed Identifier
21471821
Citation
Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AM. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc. 2011 Jun;43(6):1125-31. doi: 10.1249/MSS.0b013e31821597b4.
Results Reference
background
PubMed Identifier
17635415
Citation
Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007 Sep;191(1):59-66. doi: 10.1111/j.1748-1716.2007.01713.x. Epub 2007 Jul 17.
Results Reference
background
PubMed Identifier
19913611
Citation
Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med. 2010 Jan 15;48(2):342-7. doi: 10.1016/j.freeradbiomed.2009.11.006. Epub 2009 Nov 12.
Results Reference
background
PubMed Identifier
21284982
Citation
Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 2011 Feb 2;13(2):149-59. doi: 10.1016/j.cmet.2011.01.004.
Results Reference
background
Citation
Levi, DS, Scott V, et al. Pulmonary arterial hypertension in congenital heart disease. In: Humbert, M, Lynch, JP, Eds. Pulmonary Hypertension. New York: Informa Healthcare USA, Inc. 2010: 176-195.
Results Reference
background
PubMed Identifier
19720606
Citation
Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, Provencher S. Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax. 2010 Feb;65(2):113-7. doi: 10.1136/thx.2009.117168. Epub 2009 Aug 30.
Results Reference
background
PubMed Identifier
19389575
Citation
McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.
Results Reference
background
PubMed Identifier
11035689
Citation
Mehta NJ, Khan IA, Mehta RN, Sepkowitz DA. HIV-Related pulmonary hypertension: analytic review of 131 cases. Chest. 2000 Oct;118(4):1133-41. doi: 10.1378/chest.118.4.1133.
Results Reference
background
PubMed Identifier
19555855
Citation
Morrell NW, Adnot S, Archer SL, Dupuis J, Lloyd Jones P, MacLean MR, McMurtry IF, Stenmark KR, Thistlethwaite PA, Weissmann N, Yuan JX, Weir EK. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S20-S31. doi: 10.1016/j.jacc.2009.04.018.
Results Reference
background
PubMed Identifier
14583573
Citation
Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM, Coghlan JG. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis. 2003 Nov;62(11):1088-93. doi: 10.1136/ard.62.11.1088.
Results Reference
background
PubMed Identifier
14555558
Citation
Olschewski H, Rohde B, Behr J, Ewert R, Gessler T, Ghofrani HA, Schmehl T. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest. 2003 Oct;124(4):1294-304. doi: 10.1378/chest.124.4.1294.
Results Reference
background
PubMed Identifier
9117037
Citation
Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, Hirschel B, Luthy R. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med. 1997 Mar;155(3):990-5. doi: 10.1164/ajrccm.155.3.9117037.
Results Reference
background
PubMed Identifier
21268727
Citation
Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011 Jan 27;364(4):351-60. doi: 10.1056/NEJMra0910203. No abstract available.
Results Reference
background
PubMed Identifier
15784871
Citation
Pluta RM, Dejam A, Grimes G, Gladwin MT, Oldfield EH. Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. JAMA. 2005 Mar 23;293(12):1477-84. doi: 10.1001/jama.293.12.1477.
Results Reference
background
PubMed Identifier
21249218
Citation
Pluta RM, Oldfield EH, Bakhtian KD, Fathi AR, Smith RK, Devroom HL, Nahavandi M, Woo S, Figg WD, Lonser RR. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers. PLoS One. 2011 Jan 10;6(1):e14504. doi: 10.1371/journal.pone.0014504.
Results Reference
background
PubMed Identifier
17899625
Citation
Ranque B, Authier FJ, Berezne A, Guillevin L, Mouthon L. Systemic sclerosis-associated myopathy. Ann N Y Acad Sci. 2007 Jun;1108:268-82. doi: 10.1196/annals.1422.029.
Results Reference
background
PubMed Identifier
8988890
Citation
Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997 Jan 9;336(2):111-7. doi: 10.1056/NEJM199701093360207. No abstract available.
Results Reference
background
PubMed Identifier
15249491
Citation
Rubin LJ; American College of Chest Physicians. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004 Jul;126(1 Suppl):7S-10S. doi: 10.1378/chest.126.1_suppl.7S. No abstract available.
Results Reference
background
PubMed Identifier
19788924
Citation
Shiva S. Mitochondria as metabolizers and targets of nitrite. Nitric Oxide. 2010 Feb 15;22(2):64-74. doi: 10.1016/j.niox.2009.09.002. Epub 2009 Sep 27.
Results Reference
background
PubMed Identifier
15863633
Citation
Shorr AF, Helman DL, Davies DB, Nathan SD. Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J. 2005 May;25(5):783-8. doi: 10.1183/09031936.05.00083404.
Results Reference
background
PubMed Identifier
19555858
Citation
Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S43-S54. doi: 10.1016/j.jacc.2009.04.012.
Results Reference
background
PubMed Identifier
17932378
Citation
Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, Gressin V, Clerson P, Sereni D, Simonneau G. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008 Jan 1;177(1):108-13. doi: 10.1164/rccm.200704-541OC. Epub 2007 Oct 11.
Results Reference
background
PubMed Identifier
11890739
Citation
Smith AP, Demoncheaux EA, Higenbottam TW. Nitric oxide gas decreases endothelin-1 mRNA in cultured pulmonary artery endothelial cells. Nitric Oxide. 2002 Mar;6(2):153-9. doi: 10.1006/niox.2001.0400.
Results Reference
background
PubMed Identifier
17959632
Citation
Souza R, Humbert M, Sztrymf B, Jais X, Yaici A, Le Pavec J, Parent F, Herve P, Soubrier F, Sitbon O, Simonneau G. Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases. Eur Respir J. 2008 Feb;31(2):343-8. doi: 10.1183/09031936.00104807. Epub 2007 Oct 24. Erratum In: Eur Respir J. 2008 Apr;31(4):912.
Results Reference
background
PubMed Identifier
21448667
Citation
Tsihlis ND, Oustwani CS, Vavra AK, Jiang Q, Keefer LK, Kibbe MR. Nitric oxide inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by increasing the ubiquitination and degradation of UbcH10. Cell Biochem Biophys. 2011 Jun;60(1-2):89-97. doi: 10.1007/s12013-011-9179-3.
Results Reference
background
Citation
Tyvaso US Package Insert. Research Triangle Park, NC: United Therapeutics Corp; 2011.
Results Reference
background
PubMed Identifier
11750590
Citation
Uhlmann D, Ludwig S, Escher E, Armann B, Gabel G, Teupser D, Tannapfel A, Hauss J, Witzigmann H. Protective effect of a selective endothelin a receptor antagonist (BSF 208075) on graft pancreatitis in pig pancreas transplantation. Transplant Proc. 2001 Nov-Dec;33(7-8):3732-4. doi: 10.1016/s0041-1345(01)02523-4. No abstract available.
Results Reference
background
PubMed Identifier
21911616
Citation
Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol. 2011 Nov 15;589(Pt 22):5517-28. doi: 10.1113/jphysiol.2011.216341. Epub 2011 Sep 12.
Results Reference
background
PubMed Identifier
17045906
Citation
Voswinckel R, Enke B, Reichenberger F, Kohstall M, Kreckel A, Krick S, Gall H, Gessler T, Schmehl T, Ghofrani HA, Schermuly RT, Grimminger F, Rubin LJ, Seeger W, Olschewski H. Favorable effects of inhaled treprostinil in severe pulmonary hypertension: results from randomized controlled pilot studies. J Am Coll Cardiol. 2006 Oct 17;48(8):1672-81. doi: 10.1016/j.jacc.2006.06.062. Epub 2006 Sep 26.
Results Reference
background
Citation
Ware, JE, Kosinski, M, Dewey JE. How to Score Version Two of the SF-36 Health Survey. Lincoln, RI: QualityMetric, Incorporated, 2000.
Results Reference
background
PubMed Identifier
8823230
Citation
Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marle SP, Peeters PA, Jonkman JH, Jones CR. Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther. 1996 Aug;60(2):124-37. doi: 10.1016/S0009-9236(96)90127-7.
Results Reference
background
PubMed Identifier
15888814
Citation
Weitzenblum E, Chaouat A. Severe pulmonary hypertension in COPD: is it a distinct disease? Chest. 2005 May;127(5):1480-2. doi: 10.1378/chest.127.5.1480. No abstract available.
Results Reference
background
PubMed Identifier
10908213
Citation
Williamson DJ, Wallman LL, Jones R, Keogh AM, Scroope F, Penny R, Weber C, Macdonald PS. Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation. 2000 Jul 25;102(4):411-8. doi: 10.1161/01.cir.102.4.411.
Results Reference
background
PubMed Identifier
21177703
Citation
Zuckerbraun BS, George P, Gladwin MT. Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling. Cardiovasc Res. 2011 Feb 15;89(3):542-52. doi: 10.1093/cvr/cvq370. Epub 2010 Dec 22.
Results Reference
background

Learn more about this trial

A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)

We'll reach out to this number within 24 hrs