Idiopathic Pulmonary FibrosisPhase 2/3BUILD 1NCT00071461
Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis
A Phase 2/3 study testing bosentan in people with Idiopathic Pulmonary Fibrosis, run by Actelion at 29 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- bosentan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 29 sitesin 8 countries
- Study dates
- Aug 2003to May 2010
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Serum creatinine ≥ 2.5 mg/dl (221 mmol/l) or dialysis.
- Hemoglobin concentration < 75% the lower limit of normal ranges.
- Systolic blood pressure < 85 mm Hg.
- Pregnancy or breast-feeding.
- Current drug or alcohol dependence.
- Smoker (≥ 5 cigarettes per day) or former smoker (≥ 5 cigarettes per day) having stopped less than 6 months prior to randomization.
- Recently started (< 8 weeks from Screening visit) or planned cardio-pulmonary rehabilitation program based on exercise.
- Treatment with oral corticosteroids (> 15 mg/day prednisone or equivalent), immunosuppressive, cytotoxic or antifibrotic drugs such as TNF alpha blocker, or interferon gamma within 4 weeks of randomization.within 4 weeks of randomization.
- Treatment with glibenclamide (glyburide), cyclosporine A or tacrolimus within 1 weeks of randomization.
- Treatment with an endothelin receptor antagonist within 3 months of randomization.
- Treatment within 3 months of randomization or planned treatment with another investigational drug.
- Known hypersensitivity to bosentan or any of the excipients.
Trial locations and contacts
29 sites in 8 countries.
29 sites in 8 countries
United States16 sites
University of Michigan Health System - Division of Pulmonary & Critical Care Medicine
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham - Pulmonary Division
Birmingham, Alabama, 35294
National Jewish Medical and Research Center
Denver, Colorado, 80204
Baylor College of Medicine
Houston, Texas, 77030
University of Iowa Hospitals & Clinics - Department of Internal Medicine
Iowa City, Iowa, 52242
David Geffen School of Medicine at UCLA - Division of Pulmonary and Critical Care Medicine
Los Angeles, California, 90024
University of Wisconsin Hospitals & Clinics - Section of Pulmonary and Critical Care Medicine
Madison, Wisconsin, 53792
Jackson Memorial Hospital
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale University School of Medicine
New Haven, Connecticut, 06520
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
Mayo Medical School - Mayo Clinic
Rochester, Minnesota, 55905
UCSD Medical Center
San Diego, California, 92103
University of California - Ambulatory Care Center
San Francisco, California, 94143
University of Washington - Division of Pulmonary & Critical Care Medicine
Seattle, Washington, 98195
Canada3 sites
Notre-Dame Hospital - Clinique du Thorax
Montreal, Quebec, H2L 4M1
Rosedale Medical Center
Toronto, Ontario, M4X 1W4
University of British Columbia - St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
France3 sites
Hôpital Avicenne - Université de Paris
Bobigny
Médecine Spécialisée Aigüe - CHU Grenoble
Grenoble, 38043
Hôpital Louis Pradel
Lyon, 69000
Germany3 sites
Abt. Pneumologie Medizinische Klinik Universitätsklinikum Freiburg
Freiburg im Breisgau
Klinik Löwenstein gGmbH
Löwenstein
Medizinische Klinik und Poliklinik I Klinikum der Universität München
München
Italy1 site
Section of Respiratory Diseases - Policlinico Le Scotte - Siena University
Siena
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Bosentan in Patients With Idiopathic Pulmonary Fibrosis, Open Label Extension
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
- Being tested
- bosentan, Placebo
- Keywords
- Idiopathic pulmonary fibrosis, Interstitial lung disease, Bosentan, BUILD
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bosentanDrug
Also called Tracleer
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 6-minute walk distance
Measured: Baseline to End-of-Period 1
Secondary outcomes (1)
Death or treatment failure
Measured: Up to End-of-Period 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2003 (estimated)
- Study startAug 2003
- Primary completionSep 2005
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00071461
- Sponsor's protocol ID
- AC-052-320
- Other IDs
- BUILD 1
- Acronym
- BUILD 1
- Status last verified
- Feb 2012
- First submitted
- 23 Oct 2003
- Last updated
- 24 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19679600King 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.
PubMed 17901413
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Bosentan in Patients With Idiopathic Pulmonary Fibrosis, Open Label Extension
- ClinicalTrials.gov ID
- NCT00071461
- Acronym / sponsor ID
- BUILD 1 / AC-052-320
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Idiopathic pulmonary fibrosis, Interstitial lung disease, Bosentan, BUILD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Aug 2003
- Primary completion
- Sep 2005 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 24 Oct 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: bosentanInitial 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 | Placebo comparator | Drug: PlaceboInitial 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients over 18 years of age.
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bosentanAlso: TracleerInitial 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 | 1 |
| PlaceboInitial 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 | 2 |
Primary outcome
Change in 6-minute walk distance
Time frame: Baseline to End-of-Period 1
1 secondary outcome
Death or treatment failure
Time frame: Up to End-of-Period 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2012.
- Derived from this study: PubMed 19679600Raghu 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.
- Derived from this study: PubMed 17901413King 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing bosentan in people with Idiopathic Pulmonary Fibrosis, run by Actelion at 29 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada, France, Germany, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 6-minute walk distance (time frame: Baseline to End-of-Period 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00071461, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2012.