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

This study has been terminated.
(Terminated early dt to acquisition of Sponsor and change in corporate priorities)
Sponsor:
Information provided by (Responsible Party):
Aires Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01725256
First received: November 8, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: AIR001 (sodium nitrite inhalation solution)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Aires Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001 [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 29
Study Start Date: November 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 80mg AIR001 four times daily
80mg AIR001 nebulized four times daily for 16 weeks
Drug: AIR001 (sodium nitrite inhalation solution)
Dose arms specify dose loaded into the I-neb AAD System nebulizer
Other Names:
  • sodium nitrite inhalation solution
  • sodium nitrite
  • nitrite
Experimental: 46mg AIR001 four times daily
46mg AIR001 nebulized four times daily for 16 weeks
Drug: AIR001 (sodium nitrite inhalation solution)
Dose arms specify dose loaded into the I-neb AAD System nebulizer
Other Names:
  • sodium nitrite inhalation solution
  • sodium nitrite
  • nitrite
Experimental: 80mg AIR001 once daily
80mg AIR001 nebulized once daily for 16 weeks
Drug: AIR001 (sodium nitrite inhalation solution)
Dose arms specify dose loaded into the I-neb AAD System nebulizer
Other Names:
  • sodium nitrite inhalation solution
  • sodium nitrite
  • nitrite

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725256

  Show 25 Study Locations
Sponsors and Collaborators
Aires Pharmaceuticals, Inc.
Investigators
Principal Investigator: Adaani E Frost, M.D. Baylor College of Medicine
  More Information

Publications:

Responsible Party: Aires Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01725256     History of Changes
Other Study ID Numbers: AIR001-CS05
Study First Received: November 8, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Aires Pharmaceuticals, Inc.:
AIR001
sodium nitrite
PAH
Pulmonary Arterial Hypertension
inhaled sodium nitrite

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014