A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)
7 aprile 2014 aggiornato da: 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.
Panoramica dello studio
Stato
Terminato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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).
Tipo di studio
Interventistico
Iscrizione (Effettivo)
29
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- St. Vincent's Hospital
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Queensland
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Chermside, Queensland, Australia, 4032
- The Prince Charles Hospital
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Tasmania
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Hobart, Tasmania, Australia, 7000
- Royal Hobart Hospital
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Victoria
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Melbourne, Victoria, Australia, 3004
- The Alfred Hospital
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California
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La Jolla, California, Stati Uniti, 92037
- UCSD Medical Center
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Torrance, California, Stati Uniti, 90509
- UCLA Medical Center
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Colorado
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Aurora, Colorado, Stati Uniti, 80045
- University of Colorado Denver
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Kentucky
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Louisville, Kentucky, Stati Uniti, 40202
- Kentuckiana Pulmonary Associates
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Maryland
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Baltimore, Maryland, Stati Uniti, 21201
- University of Maryland Medical Center
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, Stati Uniti, 02111
- Tufts Medical Center
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Boston, Massachusetts, Stati Uniti, 02118
- Boston University School of Medicine
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Missouri
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St. Louis, Missouri, Stati Uniti, 63110-1093
- Washington University School of Medicine
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North Carolina
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Durham, North Carolina, Stati Uniti, 27710
- Duke University Medical Center
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Ohio
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Cincinnati, Ohio, Stati Uniti, 45267
- University of Cincinnati
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Columbus, Ohio, Stati Uniti, 43210
- The Ohio State University Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Stati Uniti, 15213
- University of Pittsburgh Medical Center
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Texas
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Dallas, Texas, Stati Uniti, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, Stati Uniti, 77030
- Baylor College of Medicine
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Virginia
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Falls Church, Virginia, Stati Uniti, 22042
- Inova Fairfax Hospital
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Wisconsin
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Milwaukee, Wisconsin, Stati Uniti, 53215
- Aurora St. Luke's Medical Center
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Budapest, Ungheria, 1083
- Gottsegen Gyorgy Hungarian
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Budapest, Ungheria, 1125
- Semmelweis Karlocai
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Debrecen, Ungheria, 4032
- University of Debrecen
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Szeged, Ungheria, 6720
- University of Szeged
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 75 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- 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
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
Exclusion Criteria:
- 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:
- 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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 80mg AIR001 four times daily
80mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Altri nomi:
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Sperimentale: 46mg AIR001 four times daily
46mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Altri nomi:
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Sperimentale: 80mg AIR001 once daily
80mg AIR001 nebulized once daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
Lasso di tempo: 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).
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16 weeks
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Time to Clinical Worsening (TTCW), other hemodynamics, and safety
Lasso di tempo: 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
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Investigatore principale: Adaani E Frost, M.D., Baylor College of Medicine
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
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Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 novembre 2012
Completamento primario (Effettivo)
1 febbraio 2014
Completamento dello studio (Effettivo)
1 febbraio 2014
Date di iscrizione allo studio
Primo inviato
8 novembre 2012
Primo inviato che soddisfa i criteri di controllo qualità
9 novembre 2012
Primo Inserito (Stima)
12 novembre 2012
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
9 aprile 2014
Ultimo aggiornamento inviato che soddisfa i criteri QC
7 aprile 2014
Ultimo verificato
1 aprile 2014
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- AIR001-CS05
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Prove cliniche su AIR001 (sodium nitrite inhalation solution)
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University of California, San FranciscoCompletato