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

April 7, 2014 updated by: Aires Pharmaceuticals, Inc.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St. Vincent's Hospital
    • Queensland
      • Chermside, Queensland, Australia, 4032
        • The Prince Charles Hospital
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Royal Hobart Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
  • Hungary
      • Budapest, Hungary, 1083
        • Gottsegen Gyorgy Hungarian
      • Budapest, Hungary, 1125
        • Semmelweis Karlocai
      • Debrecen, Hungary, 4032
        • University of Debrecen
      • Szeged, Hungary, 6720
        • University of Szeged
  • United States
    • California
      • La Jolla, California, United States, 92037
        • UCSD Medical Center
      • Torrance, California, United States, 90509
        • UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kentuckiana Pulmonary Associates
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02118
        • Boston University School of Medicine
    • Missouri
      • St. Louis, Missouri, United States, 63110-1093
        • Washington University School of Medicine
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora St. Luke's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
  • nitrite
  • sodium nitrite inhalation solution
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
  • nitrite
  • sodium nitrite inhalation solution
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
  • nitrite
  • sodium nitrite inhalation solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
Time Frame: 16 weeks
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).
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Clinical Worsening (TTCW), other hemodynamics, and safety
Time Frame: 16 weeks

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.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aires Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Adaani E Frost, M.D., Baylor College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

November 8, 2012

First Submitted That Met QC Criteria

November 9, 2012

First Posted (Estimate)

November 12, 2012

Study Record Updates

Last Update Posted (Estimate)

April 9, 2014

Last Update Submitted That Met QC Criteria

April 7, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIR001-CS05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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