Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension

NCT ID: NCT00380068

Last Updated: 2012-04-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

224 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2009-05-31

Brief Summary

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The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.

Detailed Description

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This study was to enroll up to 200 participants with PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5). Participants with left heart disease or left heart failure were excluded (WHO Group 2). Participants could be receiving prostacyclin or sildenafil therapy at baseline, and participants who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities were eligible.

Conditions

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Pulmonary Hypertension

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ambrisentan

Group Type EXPERIMENTAL

Ambrisentan

Intervention Type DRUG

Oral tablets taken once daily.

Interventions

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Ambrisentan

Oral tablets taken once daily.

Intervention Type DRUG

Other Intervention Names

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Letairis Volibris

Eligibility Criteria

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Inclusion Criteria

1. 18 years of age or older
2. Current diagnosis of PH associated with an acceptable etiology as outlined in the protocol, including: PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5).
3. Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy
4. Right heart catheterization completed prior to screening must meet pre-specified criteria
5. Female participants of childbearing potential must have a negative serum pregnancy test and must agree to use a reliable double method of contraception until study completion and for at least four weeks following their final study visit.
6. Male participants must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking ambrisentan and queried regarding his understanding of the potential risks as described in the Informed Consent Form.

Exclusion Criteria

1. Participation in a previous clinical study with ambrisentan
2. Bosentan or sitaxsentan use within four weeks prior to the screening visit
3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is greater than 3 times the upper limit of normal at the screening visit
4. Pulmonary function tests not meeting the following pre-specified criteria: 1) mean pulmonary arterial pressure (PAP) \>= 25 mm Hg; 2) PVR \> 3 mm Hg/L/min; 3) pulmonary capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) \< 15 mm Hg; 4) total lung capacity (TLC) \>= 70% of predicted normal for participants without ILD or \>= 60% of predicted normal in participants with ILD; forced expiratory volume in 1 second (FEV1) \>= 65% of predicted normal in participants without COPD or \>= 50% of predicted normal in participants with COPD
5. Contraindication to treatment with endothelin receptor antagonist (ERA)
6. History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years
7. Female participant who is pregnant or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lewis J Rubin, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Arizona Pulmonary Specialists, Ltd

Phoenix, Arizona, United States

Site Status

UCSD Medical Center, Thornton Hospital

La Jolla, California, United States

Site Status

Greater Los Angeles, VA Medical Center

Los Angeles, California, United States

Site Status

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Site Status

University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Pulmonary Hypertension Clinic Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Suncoast Lung Center

Sarasota, Florida, United States

Site Status

Medical College of Georgia

Augusta, Georgia, United States

Site Status

Atlanta Institute for Medical Research, Inc.

Decatur, Georgia, United States

Site Status

University of Chicago Hospitals

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Tufts-New England Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Adult Congenital Heart Service

Boston, Massachusetts, United States

Site Status

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

University of Medicine & Dentistry of New Jersey

Newark, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

New York Presbyterian Pulmonary Hypertension Center

New York, New York, United States

Site Status

Mary Parkes Asthma Center

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

The Lindner Clinical Trial Center

Cincinnati, Ohio, United States

Site Status

University Hospitals of Cleveland

Cleveland, Ohio, United States

Site Status

Legacy Clinical Northwest

Portland, Oregon, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Lexington Pulmonary and Critical Care

Lexington, South Carolina, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Virginia Health Sciences Center

Charlottesville, Virginia, United States

Site Status

St. Vincent's Hospital

Darlinghurst, New South Wales, Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Peter Lougheed Centre

Calgary, Alberta, Canada

Site Status

University of Alberta Hospitals

Edmonton, Alberta, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Australia Canada

Related Links

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Other Identifiers

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ARIES-3

Identifier Type: -

Identifier Source: secondary_id

AMB-323

Identifier Type: -

Identifier Source: org_study_id

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