NCT00879229

Brief Summary

Ambrisentan is an endothelin receptor antagonist used for the treatment of pulmonary hypertension (PH). Based on research suggesting a role for endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the poor prognosis for patients with IPF who are also diagnosed with PH, this study was designed to evaluate the effectiveness and safety of ambrisentan in that patient population.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jul 2009

Geographic Reach
6 countries

82 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 9, 2009

Completed
3 months until next milestone

Study Start

First participant enrolled

July 1, 2009

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2011

Completed
3.2 years until next milestone

Results Posted

Study results publicly available

April 22, 2014

Completed
Last Updated

May 15, 2014

Status Verified

May 1, 2014

Enrollment Period

1.6 years

First QC Date

April 8, 2009

Results QC Date

August 9, 2013

Last Update Submit

May 5, 2014

Conditions

Keywords

Idiopathic Pulmonary FibrosisPulmonary HypertensionPHIPFAmbrisentanERAEndothelin Receptor AntagonistCardiovascular

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in Six-minute Walk Distance (6MWD).

    The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.

    Baseline to Week 16

Secondary Outcomes (9)

  • Long-term Survival

    Week 48

  • Transition Dyspnea Index (TDI)

    Baseline to Week 16

  • Change From Baseline in WHO Functional Class

    Baseline to Week 16

  • Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted

    Baseline to Week 16

  • Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)

    Baseline to Week 16

  • +4 more secondary outcomes

Study Arms (2)

Ambrisentan

EXPERIMENTAL

Participants were randomized to receive ambrisentan treatment at an initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 52 weeks

Drug: Ambrisentan

Placebo

PLACEBO COMPARATOR

Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.

Drug: AmbrisentanDrug: Placebo

Interventions

Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.

Also known as: Letairis
AmbrisentanPlacebo

Placebo to match ambrisentan administered orally once daily.

Placebo

Eligibility Criteria

Age35 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Weight ≥ 40 kg at screening
  • Diagnosis of IPF based on modified American Thoracic Society-European Respiratory Society guidelines
  • Diagnosis of PH based on the following hemodynamic requirements: mean pulmonary artery pressure (mPAP ≥ 25 mm Hg; pulmonary vascular resistance \> 240 dyne.sec/cm\^5; pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mm Hg
  • Forced vital capacity (FVC) ≥ 40%
  • Able to walk at least 50 meters during two 6-minute walk tests
  • If receiving calcium channel blockers, low-dose oral corticosteroids, immunosuppressive, cytoxic, or antifibrotic drugs dose must have been stable.

You may not qualify if:

  • Diagnosis of PH primarily due to an etiology other than IPF
  • Surgical lung biopsy diagnosis other than Usual Interstitial Pneumonia
  • Other known cause of interstitial lung disease
  • Evidence of significant obstructive lung disease
  • Recent hospitalization for an acute exacerbation of IPF
  • Recent active pulmonary or upper respiratory tract infection
  • Left ventricular ejection fraction \< 40%
  • Serum creatinine ≥ 2.5 mg/dL
  • Required hemodialysis, peritoneal dialysis, or hemofiltration
  • Female subject who was pregnant or breastfeeding
  • Recent treatment for PH with an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, or prostacyclin derivative
  • Recent treatment with high dose oral corticosteroids
  • Recent treatment (within 4 weeks prior to screening) with imatinib mesylate (Gleevec)
  • Alanine aminotransferase or aspartate aminotransferase lab value that was greater than 1.5 x the upper limit of the normal range
  • Discontinued other ERA treatment for any adverse reaction other than those associated with liver function test abnormalities

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (85)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California Davis

Davis, California, 95817, United States

Location

David Geffen School of Medicine UCLA

Los Angeles, California, 90095, United States

Location

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado Heatlh Sciences Center

Aurora, Colorado, 80045, United States

Location

Bay Area Chest Physicians

Clearwater, Florida, 33756, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami Medical Center

Miami, Florida, 33136, United States

Location

Suncoast Lung Center

Sarasota, Florida, 34233, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Atlanta Institute for Medical Research

Decatur, Georgia, 30030, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Kentuckiana Pulmonary Association

Louisville, Kentucky, United States

Location

Maine Medical Center

Portland, Maine, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deacones Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Creighton University Center for Allergy & Asthma

Omaha, Nebraska, 68131, United States

Location

Dartmouth Medical School

Lebanon, New Hampshire, 03756, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

North Shore Health System

New Hyde Park, New York, 11040, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Lindner Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University Hospitals of Cleveland Case Western

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Alleghany General Hospital

Pittsburgh, Pennsylvania, 12512, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Inova Heart Institiute and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Providence Everett Medical Center

Everett, Washington, 98201, United States

Location

St. Vincents Hospital

Sydney, New South Wales, 2010, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Medizinische Universität Graz

Graz, 8036, Austria

Location

Universitatsklinikum Innsbruck

Innsbruck, Austria

Location

Medizinische Universität Wien

Vienna, 1090, Austria

Location

Peter Loughheed Center- Calgary General Hospital

Calgary, Alberta, T1Y 6J4, Canada

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Toronto General Hospital

Toronto, Ontario, Canada

Location

Centre Hospitalier De L'Universite de Montreal

Montreal, Quebec, H2W 1T8, Canada

Location

Sir Mortimer B. Davis Jewish General Center

Montreal, Quebec, Canada

Location

Centre de Pneumologie de L'Hospital Laval

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Charite-Universitatsmedizin Berlin

Berlin, Germany

Location

Krankenhaus Donaustauf der LVA

Donaustauf, 93093, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79095, Germany

Location

Universitat Greifswald

Greifswald, 17475, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Thorax Klinik

Heidelberg, 66126, Germany

Location

LMU Klinikum der Universitat

München, Germany

Location

Azienda Ospedaliero Universitaria

Catania, Italy

Location

Presidio Ospedaliero G.B. Morgagni

Forlì, Italy

Location

Ospedale S.Giuseppe Fatebenefratelli

Milan, Italy

Location

Unita Funzionale di Pneumologia e Fisiopatologia Respiratoria

Milan, 20132, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

Instituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione

Palermo, Italy

Location

Policlinico Universitario Tor Vergata

Rome, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

Centro delle Interstiziopatie Polmonari e Malattie Rare del Polmone

Torino, 10043, Italy

Location

Papworth Hospital NHS Foundation Trust

Cambridge, CB23 3RE, United Kingdom

Location

University Hospital Aintree

Liverpool, United Kingdom

Location

University College Hosptial

London, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

Related Publications (1)

  • Ruocco G, Cekorja B, Rottoli P, Refini RM, Pellegrini M, Di Tommaso C, Del Castillo G, Franci B, Nuti R, Palazzuoli A. Role of BNP and echo measurement for pulmonary hypertension recognition in patients with interstitial lung disease: An algorithm application model. Respir Med. 2015 Mar;109(3):406-15. doi: 10.1016/j.rmed.2014.12.011. Epub 2015 Jan 3.

MeSH Terms

Conditions

Idiopathic Pulmonary FibrosisHypertension, Pulmonary

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Pulmonary FibrosisLung Diseases, InterstitialLung DiseasesRespiratory Tract DiseasesHypertensionVascular DiseasesCardiovascular Diseases

Limitations and Caveats

Study GS-US-300-0128 was terminated early with enrollment of 40 of 225 planned subjects.

Results Point of Contact

Title
Clinical Trial Disclosures
Organization
Gilead Sciences, Inc.

Study Officials

  • Hunter Gillies, M.D.

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2009

First Posted

April 9, 2009

Study Start

July 1, 2009

Primary Completion

February 1, 2011

Study Completion

February 1, 2011

Last Updated

May 15, 2014

Results First Posted

April 22, 2014

Record last verified: 2014-05

Locations