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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01725256




Registration number
NCT01725256
Ethics application status
Date submitted
8/11/2012
Date registered
12/11/2012
Date last updated
9/04/2014

Titles & IDs
Public title
A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)
Scientific 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)
Secondary ID [1] 0 0
AIR001-CS05
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AIR001 (sodium nitrite inhalation solution)

Experimental: 80mg AIR001 four times daily - 80mg AIR001 nebulized four times daily for 16 weeks

Experimental: 46mg AIR001 four times daily - 46mg AIR001 nebulized four times daily for 16 weeks

Experimental: 80mg AIR001 once daily - 80mg AIR001 nebulized once daily for 16 weeks


Treatment: Drugs: AIR001 (sodium nitrite inhalation solution)
Dose arms specify dose loaded into the I-neb AAD System nebulizer
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
Time to Clinical Worsening (TTCW), other hemodynamics, and safety
Timepoint [1] 0 0
16 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
Hungary
State/province [14] 0 0
Debrecen
Country [15] 0 0
Hungary
State/province [15] 0 0
Szeged

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Aires Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01725256
Trial related presentations / publications
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Public notes

Contacts
Principal investigator
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Adaani E Frost, M.D.
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Baylor College of Medicine
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Contact person for public queries
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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01725256