A Phase 2, Multi-Centre, unblinded, parallel dose, safety and effectiveness study of AIR001 in subjects with high blood pressure in the blood vessels in the lungs

• Conditions: Pulmonary Arterial Hypertension; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2012-000166-37-CZ
• Lead Sponsor: Aires Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11-20
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-mandated procedures.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Has a current diagnosis of symptomatic PAH classified by one of the following:
a. Idiopathic (IPAH) or heritable pulmonary arterial hypertension (HPAH); or
b. PAH associated with one of the following CTD:
i. Systemic sclerosis (scleroderma);
ii. Limited scleroderma;
iii. Mixed connective tissue disease;
iv. Systemic lupus erythematosus;
v. Overlap syndrome.
c. PAH associated with:
i. HIV infection;
ii. Simple, congenital systemic-to-pulmonary shunts at least one year post surgical repair.
iii. Exposure to legal drugs, chemicals and toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil or L-tryptophan. Subjects with PAH associated with illegal drug use, such as methamphetamine, are excluded.
4. Has a cardiac catheterization prior to Screening that is consistent with the diagnosis of PAH meeting all of the following criteria:
a. mPAP = 25 mmHg (at rest);
b. PCWP = 15 mmHg; and
c. If PCWP is not available, then mean left atrial pressure (mLAP) or left ventricular-end diastolic pressure (LVEDP) = 15 mmHg in the absence of left atrial obstruction;
c. PVR > 3 mmHg/Liter (L)/minute (min) or 240 dyn.sec/cm.
5. A qualification cardiac catheterization is required, to confirm the persistence and severity of PAH, if the diagnostic catheterization was performed more than 1 month (30 days) prior to Baseline/Day 1 (see criteria in Inclusion Criteria #4). This catheterization will serve to
provide Baseline hemodynamic values for further efficacy analysis. A cardiac catheterization performed within 1 month (30 days) prior to Baseline/Day 1, per the subject standard medical care (not for the purposes of this study) can be used in lieu of repeating the test, if all
the following criteria are met:
a. Confirms diagnosis as per the required data points (PVR, CO, CI, mPAP, mRAP, PCWP, SVR, and SvO 2 );
b. The subject has a PVR above 300 dyn.sec/cm on the catheterization used to qualify the subject for the study; and
c. No change in disease-specific PAH therapy has occurred since the catheterization used to qualify the subject for the study.
6. Newly diagnosed PAH on no disease-specific PAH therapy or previously diagnosed with PAH on stable (i.e. 3 months (90 days) prior to the Baseline qualification cardiac catheterization) oral disease-specific PAH therapy with either an ETRA and/or PDE-5i. Every attempt should be made to maintain the dose of these agents throughout the study. The use of PDE-5i as needed for erectile dysfunction (ED) is permitted as long as the subject has not taken a dose within 48-hours of any Baseline or study related efficacy assessment. In addition, the subject must not take more than 8 sildenafil tablets, 6 vardenafil, or 4 tadalafil tablets per month for ED.
7. Has PFTs within 6 months (180 days) prior to Baseline/Day 1 with no evidence of significant parenchymal lung disease. Parenchymal lung disease is defined as:
• Forced expiratory volume in 1 second (FEV 1 ) = 70% (predicted);
• Forced expiratory volume in 1 second/forced vital capacit

Exclusion Criteria

1.Participation in a device or other interventional clinical studies, with the exception of studies utilizing AIR001, within 1 month (30 days) of Baseline/Day 1 and/or during study participation.
2. Participation in a cardio-pulmonary rehabilitation program based upon exercise within 1 month (30 days) prior to Baseline/Day 1 and/or during study participation.
3. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mmHg or sitting diastolic blood pressure >100 mmHg during Screening.
4. Sitting systolic BP < 90 mmHg at Screening or Baseline/Day 1.
5. History of orthostatic hypotension or at the time of Screening demonstrates orthostatic hypotension defined as a drop in systolic BP by = 20 mmHg or diastolic BP of = 10 mmHg or the development of significant postural symptoms (syncope, near syncope, lightheadedness, or vertigo) when going from the supine to the standing position as assessed during Screening assessment.
6.Has history of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency;
b.Pericardial constriction;
c. Restrictive or congestive cardiomyopathy;
d. Left ventricular ejection fraction < 40% by multiple gated acquisition scan (MUGA), angiography or echocardiography (ECHO) prior to Screening;
e. Left ventricular shortening fraction < 22% by ECHO prior to Screening;
f. Symptomatic coronary disease.
7. Significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation.
8. Acutely decompensated heart failure within 1 month (30 days) prior to Baseline/Day 1.
9. History of atrial septostomy within 6 months (180 days) prior to Baseline/Day 1.
10. History of obstructive sleep apnea (treated, untreated or resolved).
11. Diagnosis of Down syndrome.
12. Moderate to severe hepatic impairment classified as a Child-Pugh Class B or C at Screening.
13. Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an estimated Glomular Filtration Rate (eGFR) < 30 mL/min at Screening, or requires dialytic support.
14. Has a hemoglobin (Hgb) concentration < 8.5 g/dL at Screening.
15. Personal or family history of the following:
a. Congenital or acquired methemoglobinemia;
b. RBC CYPB5 reductase deficiency.
16. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication to receiving methylene blue.
17. For subjects with HIV associated PAH, any of the following:
• Concomitant active opportunistic infections within 6 months (180 days) prior to Screening;
• Detectable viral load within 3 months (90 days) of Screening;
• Cluster designation 4 (CD4+) T-cell count < 200 mm within 3 months of Screening;
• Changes in antiretroviral regimen within 3 months of Screening;
• Using inhaled pentamidine.
18. Receiving chronic treatment with prostacyclin/prostacyclin analogue within 2 months of Baseline/Day 1. Use of prostacyclin for acute vasodilator testing during cardiac catheterization is allowed.
19. Requirement of intravenous inotropes within 1 month (30 days) prior to Baseline/Day 1.
20. The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 1 month (30 days) prior to Baseline/Day 1 or througho

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified