Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension

Last updated: April 2, 2012
Sponsor: Gilead Sciences
Overall Status: Completed

Phase

3

Condition

Williams Syndrome

Stress

Scleroderma

Treatment

N/A

Clinical Study ID

NCT00380068
AMB-323
ARIES-3
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Summarized Inclusion Criteria:

  1. 18 years of age or older

  2. Current diagnosis of PH associated with an acceptable etiology as outlined in theprotocol, including: PH due to the following etiologies: 1) PAH including idiopathicand familial PAH and PAH associated with collagen vascular disease, congenitalsystemic-to-pulmonary shunts (including Eisenmenger's syndrome), humanimmunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogenstorage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1);

  1. PH associated with lung diseases and/or hypoxemia, including chronic obstructivepulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing,and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distalchronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHOGroup 5).
  1. Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calciumchannel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductaseinhibitor therapy

  2. Right heart catheterization completed prior to screening must meet pre-specifiedcriteria

  3. Female participants of childbearing potential must have a negative serum pregnancytest and must agree to use a reliable double method of contraception until studycompletion and for at least four weeks following their final study visit.

  4. Male participants must be informed of the potential risks of testicular tubularatrophy and infertility associated with taking ambrisentan and queried regarding hisunderstanding of the potential risks as described in the Informed Consent Form.

Exclusion

Summarized 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 isgreater than 3 times the upper limit of normal at the screening visit

  4. Pulmonary function tests not meeting the following pre-specified criteria: 1) meanpulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonarycapillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participantswithout ILD or >= 60% of predicted normal in participants with ILD; forced expiratoryvolume 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 situcarcinoma of the cervix within the past five years

  7. Female participant who is pregnant or breastfeeding

Study Design

Total Participants: 224
Study Start date:
August 01, 2006
Estimated Completion Date:
May 31, 2009

Study Description

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.

Connect with a study center

  • St. Vincent's Hospital

    Darlinghurst, New South Wales 2010
    Australia

    Site Not Available

  • Royal Perth Hospital

    Perth, 6000
    Australia

    Site Not Available

  • Peter Lougheed Centre

    Calgary, Alberta T1Y 6J4
    Canada

    Site Not Available

  • University of Alberta Hospitals

    Edmonton, Alberta T6G 2B7
    Canada

    Site Not Available

  • London Health Sciences Centre, Victoria Hospital

    London, Ontario N6A 4W9
    Canada

    Site Not Available

  • Toronto General Hospital

    Toronto, Ontario M5G 2N2
    Canada

    Site Not Available

  • University of Alabama at Birmingham

    Birmingham, Alabama 35294
    United States

    Site Not Available

  • Arizona Pulmonary Specialists, Ltd

    Phoenix, Arizona 85013
    United States

    Site Not Available

  • UCSD Medical Center, Thornton Hospital

    La Jolla, California 92037
    United States

    Site Not Available

  • Greater Los Angeles, VA Medical Center

    Los Angeles, California 90073
    United States

    Site Not Available

  • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

    Torrance, California 90502
    United States

    Site Not Available

  • University of Colorado Health Sciences Center

    Aurora, Colorado 80045
    United States

    Site Not Available

  • University of Colorado Health Science Center

    Denver, Colorado 80262
    United States

    Site Not Available

  • University of Connecticut Health Center

    Farmington, Connecticut 06030
    United States

    Site Not Available

  • Yale University School of Medicine

    New Haven, Connecticut 06520
    United States

    Site Not Available

  • Pulmonary Hypertension Clinic Mount Sinai Medical Center

    Miami Beach, Florida 33140
    United States

    Site Not Available

  • Suncoast Lung Center

    Sarasota, Florida 34233
    United States

    Site Not Available

  • Medical College of Georgia

    Augusta, Georgia 30912
    United States

    Site Not Available

  • Atlanta Institute for Medical Research, Inc.

    Decatur, Georgia 30030
    United States

    Site Not Available

  • University of Chicago Hospitals

    Chicago, Illinois 60637
    United States

    Site Not Available

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa 52242
    United States

    Site Not Available

  • Johns Hopkins University

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • Boston Adult Congenital Heart Service

    Boston, Massachusetts 02115
    United States

    Site Not Available

  • Boston University School of Medicine

    Boston, Massachusetts 02118
    United States

    Site Not Available

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Site Not Available

  • Tufts-New England Medical Center

    Boston, Massachusetts 02111
    United States

    Site Not Available

  • Wayne State University

    Detroit, Michigan 48201
    United States

    Site Not Available

  • Mayo Clinic

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • Washington University School of Medicine

    St. Louis, Missouri 63110
    United States

    Site Not Available

  • UMDNJ Scleroderma Program

    New Brunswick, New Jersey 08903
    United States

    Site Not Available

  • Newark Beth Israel Medical Center

    Newark, New Jersey 07112
    United States

    Site Not Available

  • University of Medicine & Dentistry of New Jersey

    Newark, New Jersey 07103
    United States

    Site Not Available

  • New York Presbyterian Pulmonary Hypertension Center

    New York, New York 10032
    United States

    Site Not Available

  • Mary Parkes Asthma Center

    Rochester, New York 14623
    United States

    Site Not Available

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Site Not Available

  • The Lindner Clinical Trial Center

    Cincinnati, Ohio 45219
    United States

    Site Not Available

  • University Hospitals of Cleveland

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • Legacy Clinical Northwest

    Portland, Oregon 97210
    United States

    Site Not Available

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania 15212
    United States

    Site Not Available

  • University of Pittsburgh Medical Center Presbyterian

    Pittsburgh, Pennsylvania 15213
    United States

    Site Not Available

  • Rhode Island Hospital

    Providence, Rhode Island 02903
    United States

    Site Not Available

  • Lexington Pulmonary and Critical Care

    Lexington, South Carolina 29072
    United States

    Site Not Available

  • Vanderbilt University Medical Center

    Nashville, Tennessee 37232
    United States

    Site Not Available

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Site Not Available

  • Uthsc-Sa

    San Antonio, Texas 78229
    United States

    Site Not Available

  • University of Virginia Health Sciences Center

    Charlottesville, Virginia 22908
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.