Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension

NCT00380068 | Completed Phase 3 Results DMC

• 2 other identifiers: AMB-323ARIES-3
• Study Type: interventional
• Target: 224
• Locations: 3 countries
• Sites: 39

Brief 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.

Conditions

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)

  Baseline to Week 24

Secondary Outcomes (16)

• Change From Baseline to Week 24 in Borg Dyspnea Index

  Baseline to Week 24

• Change From Baseline to Week 48 in Borg Dyspnea Index

  Baseline to Week 48

• Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)

  Baseline to Week 24

• Percent Change From Baseline to Week 48 in BNP

  Baseline to Week 48

• Change From Baseline to Week 24 in WHO Functional Class

  Baseline to Week 24

Study Arms (1)

Ambrisentan

EXPERIMENTAL

Drug: Ambrisentan

Interventions

Ambrisentan DRUG

Oral tablets taken once daily.

Also known as: Letairis, Volibris

Ambrisentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• 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).
• 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
• Right heart catheterization completed prior to screening must meet pre-specified criteria
• 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.
• 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.

You may not qualify if:

• Participation in a previous clinical study with ambrisentan
• Bosentan or sitaxsentan use within four weeks prior to the screening visit
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is greater than 3 times the upper limit of normal at the screening visit
• 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
• Contraindication to treatment with endothelin receptor antagonist (ERA)
• History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years
• Female participant who is pregnant or breastfeeding

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (39)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Pulmonary Specialists, Ltd

Phoenix, Arizona, 85013, United States

Location

UCSD Medical Center, Thornton Hospital

La Jolla, California, 92037, United States

Location

Greater Los Angeles, VA Medical Center

Los Angeles, California, 90073, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Pulmonary Hypertension Clinic Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Suncoast Lung Center

Sarasota, Florida, 34233, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Atlanta Institute for Medical Research, Inc.

Decatur, Georgia, 30030, United States

Location

University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Adult Congenital Heart Service

Boston, Massachusetts, 02115, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Medicine & Dentistry of New Jersey

Newark, New Jersey, 07103, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

New York Presbyterian Pulmonary Hypertension Center

New York, New York, 10032, United States

Location

Mary Parkes Asthma Center

Rochester, New York, 14623, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Lindner Clinical Trial Center

Cincinnati, Ohio, 45219, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Legacy Clinical Northwest

Portland, Oregon, 97210, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Lexington Pulmonary and Critical Care

Lexington, South Carolina, 29072, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Virginia Health Sciences Center

Charlottesville, Virginia, 22908, United States

Location

St. Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Royal Perth Hospital

Perth, 6000, Australia

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y 6J4, Canada

Location

University of Alberta Hospitals

Edmonton, Alberta, T6G 2B7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Related Links

• Related Info

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Martine Allard, PhD; Senior Clinical Research Scientist
• Organization: Gilead Sciences Inc

martine.allard@gilead.com

650-524-3898

Study Officials

• Lewis J Rubin, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2006
• First Posted: September 25, 2006
• Study Start: August 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: May 1, 2009
• Last Updated: April 5, 2012
• Results First Posted: November 19, 2010

Record last verified: 2012-04

Locations

AU (2); CA (3); US (34)