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Pulmonary Arterial HypertensionPhase 2NCT01725256

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

A Phase 2 study testing AIR001 (sodium nitrite inhalation solution) in people with Pulmonary Arterial Hypertension, run by Aires Pharmaceuticals, Inc. at 25 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
AIR001 (sodium nitrite inhalation solution)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
25 sitesin 3 countries
Study dates
Nov 2012to Feb 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 27Show fewer
  • 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

Who cannot join

  • 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:
Show all 39Show fewer
  • 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

Trial locations and contacts

25 sites in 3 countries.

25 sites in 3 countries

United States17 sites

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Boston University School of Medicine

    Boston, Massachusetts, 02118

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • The Ohio State University Medical Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Baylor College of Medicine

    Houston, Texas, 77030

  • UCSD Medical Center

    La Jolla, California, 92037

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Washington University School of Medicine

    St Louis, Missouri, 63110-1093

  • UCLA Medical Center

    Torrance, California, 90509

Other trials in United States

Australia4 sites

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

  • St. Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • The Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

Hungary4 sites

  • Gottsegen Gyorgy Hungarian

    Budapest, 1083

  • Semmelweis Karlocai

    Budapest, 1125

  • University of Debrecen

    Debrecen, 4032

  • University of Szeged

    Szeged, 6720

Other trials in Hungary

About this study

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)

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.

Read the 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).

Being tested
AIR001 (sodium nitrite inhalation solution)
Keywords
AIR001, sodium nitrite, PAH, Pulmonary Arterial Hypertension, inhaled sodium nitrite
Medical subject headings
Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AIR001 (sodium nitrite inhalation solution)Drug

    Also called sodium nitrite inhalation solution, sodium nitrite, nitrite

    Dose arms specify dose loaded into the I-neb AAD System nebulizer

Study groups in NCT01725256
Study groupRoleWhat they receive
80mg AIR001 four times dailyExperimental80mg AIR001 nebulized four times daily for 16 weeks
Receives: Drug: AIR001 (sodium nitrite inhalation solution)
46mg AIR001 four times dailyExperimental46mg AIR001 nebulized four times daily for 16 weeks
Receives: Drug: AIR001 (sodium nitrite inhalation solution)
80mg AIR001 once dailyExperimental80mg AIR001 nebulized once daily for 16 weeks
Receives: Drug: AIR001 (sodium nitrite inhalation solution)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 16 weeks

Secondary outcomes (1)

  1. 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.

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

Why it stopped: Terminated early dt to acquisition of Sponsor and change in corporate priorities

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01725256
Sponsor's protocol ID
AIR001-CS05
Status last verified
Apr 2014
First submitted
8 Nov 2012
Last updated
9 Apr 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17544026

  • 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.

    PubMed 21436585

  • 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.

    PubMed 12091180

  • 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.

    PubMed 19555859

  • 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.

    PubMed 19661447

  • 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.

    PubMed 21225278

  • 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.

    PubMed 16740981

  • 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.

    PubMed 8989070

  • 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.

    PubMed 25696328

  • 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.

    PubMed 17010807

  • 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.

    PubMed 15831842

  • 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.

    PubMed 8035319

  • 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.

    PubMed 14595407

  • 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.

    PubMed 17893272

  • 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.

    PubMed 15483284

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AIR001 (sodium nitrite inhalation solution) in people with Pulmonary Arterial Hypertension, run by Aires Pharmaceuticals, Inc. at 25 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Australia, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Terminated early dt to acquisition of Sponsor and change in corporate priorities). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001 (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01725256, which also lists 62 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2014.

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