Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis

NCT00071461 | Completed Phase 2 DMC

• 2 other identifiers: AC-052-320BUILD 1
• Study Type: interventional
• Target: 158
• Locations: 8 countries
• Sites: 29

Brief Summary

Endothelin-1 (ET-1) is expressed in a variety of pulmonary pathological conditions including pulmonary vascular disease and pulmonary fibrosis. Bosentan (an oral dual ET-1 receptor antagonist) could delay the progression of idiopathic pulmonary fibrosis (IPF), a condition for which no established treatment is available. The present trial investigates a possible use of bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH) WHO class III and IV, to a new category of patients suffering from IPF. It was decided to offer Open Label treatment (bosentan) for patients willing to continue in the BUILD 1 study.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Idiopathic pulmonary fibrosis; Interstitial lung disease; Bosentan; BUILD

Outcome Measures

Primary Outcomes (1)

• Change in 6-minute walk distance

  Baseline to End-of-Period 1

Secondary Outcomes (1)

• Death or treatment failure

  Up to End-of-Period 1

Study Arms (2)

1

EXPERIMENTAL

Initial dose: 62.5 mg b.i.d. for 4 weeks. * Target dose: - body weight \> 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated). * body weight \< 40 kg (90 lb): 62.5 mg b.i.d.

Drug: bosentan

2

PLACEBO COMPARATOR

Initial dose: 62.5 mg b.i.d. for 4 weeks. * Target dose: - body weight \> 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated). * body weight \< 40 kg (90 lb): 62.5 mg b.i.d.

Drug: Placebo

Interventions

bosentan DRUG

Initial dose: 62.5 mg b.i.d. for 4 weeks. * Target dose: - body weight \> 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated). * body weight \< 40 kg (90 lb): 62.5 mg b.i.d.

Also known as: Tracleer

1

Placebo DRUG

Initial dose: 62.5 mg b.i.d. for 4 weeks. * Target dose: - body weight \> 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated). * body weight \< 40 kg (90 lb): 62.5 mg b.i.d.

2

Eligibility Criteria

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

You may qualify if:

• Male or female patients over 18 years of age.
• Women must be either postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
• Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
• IPF proven diagnosis \< 3 years documented according to ATS/ERS international multidisciplinary consensus, with or without surgical (thoracoscopic or open) chest lung biopsy
• Duration of illness ≥ 3 months.
• Six-minute walk test distance (limited by dyspnea) ≥ 150 meters and \< 500 meters
• Patients who have signed the informed consent form prior to initiation of any study procedure.

You may not qualify if:

• Interstitial lung disease due to conditions other than IPF, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans with organizing pneumonia, and cancer.
• History of clinically significant environmental exposure known to cause pulmonary fibrosis (drugs, asbestos, beryllium, radiation, domestic birds, etc.).
• Severe concomitant illness limiting life expectancy (\< 1 year).
• FVC ≥ 90% predicted.
• Severe restrictive lung disease: FVC \< 50% predicted or FVC \< 1.2 l, or DLco \< 30% predicted or residual volume ≥ 120% predicted.
• Severe obstructive lung disease: FEV1/FVC\< 0.65.
• Documented improvement of patient's condition within 12 months prior to randomization with or without IPF-specific therapy (e.g., corticosteroids, immunosuppressive, cytotoxic or antifibrotic drugs, TNFa blocker, interferon g).
• Recent pulmonary or upper respiratory track infection (within 4 weeks of randomization).
• PaO2 \< 55 mm Hg (sea level) or 50 mm Hg (altitude) at rest on room air.
• Echocardiographic evidence of severe pulmonary hypertension (PH): systolic pulmonary pressure ≥ 50 mm Hg or tricuspid regurgitation velocity ≥ 3.2 m/sec (unless severe PH is invalidated by a right heart catheterization). If the pulmonary pressure is not quantifiable, presence of significant right ventricular enlargement or hypertrophy or right ventricular dysfunction.
• Severe chronic heart failure, e.g., NYHA class III or IV and/or left ventricular ejection fraction \< 25%.
• Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements, e.g., the 6MWT or the PFTs.
• (e.g., angina pectoris, intermittent claudicating, chronic arthritis).
• Baseline values of liver transaminases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) \> 3 times the upper limit of normal ranges.
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.

Sponsors & Collaborators

• Actelion: lead

Study Sites (29)

University of Alabama at Birmingham - Pulmonary Division

Birmingham, Alabama, 35294, United States

Location

David Geffen School of Medicine at UCLA - Division of Pulmonary and Critical Care Medicine

Los Angeles, California, 90024, United States

Location

UCSD Medical Center

San Diego, California, 92103, United States

Location

University of California - Ambulatory Care Center

San Francisco, California, 94143, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80204, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

University of Iowa Hospitals & Clinics - Department of Internal Medicine

Iowa City, Iowa, 52242, United States

Location

University of Michigan Health System - Division of Pulmonary & Critical Care Medicine

Ann Arbor, Michigan, 48109, United States

Location

Mayo Medical School - Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Washington - Division of Pulmonary & Critical Care Medicine

Seattle, Washington, 98195, United States

Location

University of Wisconsin Hospitals & Clinics - Section of Pulmonary and Critical Care Medicine

Madison, Wisconsin, 53792, United States

Location

University of British Columbia - St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Rosedale Medical Center

Toronto, Ontario, M4X 1W4, Canada

Location

Notre-Dame Hospital - Clinique du Thorax

Montreal, Quebec, H2L 4M1, Canada

Location

Hôpital Avicenne - Université de Paris

Bobigny, France

Location

Médecine Spécialisée Aigüe - CHU Grenoble

Grenoble, 38043, France

Location

Hôpital Louis Pradel

Lyon, 69000, France

Location

Abt. Pneumologie Medizinische Klinik Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Klinik Löwenstein gGmbH

Löwenstein, Germany

Location

Medizinische Klinik und Poliklinik I Klinikum der Universität München

München, Germany

Location

Sheba Medical Center

Tel Litwinsky, Israel

Location

Section of Respiratory Diseases - Policlinico Le Scotte - Siena University

Siena, Italy

Location

Inselspital

Bern, Switzerland

Location

Royal Brompton Hospital

London, United Kingdom

Location

Related Publications (2)

• Raghu G, King TE Jr, Behr J, Brown KK, du Bois RM, Leconte I, Roux S, Swigris J. Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1). Eur Respir J. 2010 Jan;35(1):118-23. doi: 10.1183/09031936.00188108. Epub 2009 Aug 13.

  PMID: 19679600 DERIVED

• King TE Jr, Behr J, Brown KK, du Bois RM, Lancaster L, de Andrade JA, Stahler G, Leconte I, Roux S, Raghu G. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Jan 1;177(1):75-81. doi: 10.1164/rccm.200705-732OC. Epub 2007 Sep 27.

  PMID: 17901413 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2003
• First Posted: October 24, 2003
• Study Start: August 1, 2003
• Primary Completion: September 1, 2005
• Study Completion: May 1, 2010
• Last Updated: February 24, 2012

Record last verified: 2012-02

Locations

CH (1); IT (1); DE (3); GB (1); IL (1); FR (3); CA (3); US (16)