BUILD 3: Bosentan Use in Interstitial Lung Disease (BUILD 3)

Effects of Bosentan on Morbidity and Mortality in Patients With Idiopathic Pulmonary Fibrosis - a Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Group Sequential, Phase III Study.

BUILD 3 is a prospective, multicenter, randomized, double-blind, parallel group, placebo-controlled, event-driven, group sequential, phase III superiority study. The primary objective is to demonstrate that bosentan delays disease worsening or death in patients with Idiopathic Pulmonary Fibrosis.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Bosentan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 616
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Public Hospital, Lung Transplantation & Respiratory Medicine
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital - Lung Transplant, Thoraic Dept.
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital-Respiratory Clinical Trials Unit
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital; Advanced Lung Disease Unit
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz-Klinische Abteilung für Pulmonologie
  • Grimmenstein, Austria, 2840
    • Landesklinikum Thermenregion Hochegg
  • Innsbruck, Austria, 6020
    • Medical University of Innsbruck-Div. of Clinical & Internal Medicine
  • Wien, Austria, 1090
    • Medical University of Vienna and AKH-Div of Pulmonology
  • Wien, Austria, 1140
    • Otto-Wagner Spital Wien
• Belgium
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Walter C. Mackenzie Health Sciences Centre-Univeristy of Alberta
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • The Health Care Corporation of St. John's-Eastern Health
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • London, Ontario, Canada, N6A 4G5
      • Lawson Health Research Institute
    • Toronto, Ontario, Canada, M4X 1W4
      • Toronto General Hospital-Rosedale Medical Center PFT Lab
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre Dame - Centre Hospitalier de L'Universit de Montreal
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • Institut de Cardiologie et de Pneumologie de l'Universite Laval
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital for Lung Disease "Jordanovac"
• Czech Republic
  • Olomouc, Czech Republic, 775 20
    • University Hospital Olomouc - Dept of Respiratory Disease-IP Pavlova
  • Praha 4, Czech Republic, 140 59
    • Thomayer Faculty Hospital Prague-Dept of Respiratory Disease
  • Praha 8, Czech Republic, 180 81
    • University Hospital Na Bulovce
• France
  • Bobigny, France, 93009
    • Hopital Avicenne
  • Bron, France, 69677
    • Hopital Louis Pradel
  • Grenoble, France, 38100
    • HYLAB, Clinique du Mail
  • Lille Cedex, France, 59037
    • CHRU de Lille-Hôpital Albert Calmette
  • Montpellier, France, 34295
    • CHU Hôpital Arnaud de Villeneuve
  • Paris, France, 75877
    • Hôpital Bichat
• Germany
  • Berlin, Germany, D-14165
    • Helios Klinikum Emil Von Behring
  • Coswig, Germany
    • Fachkrankenhaus Coswig; Centre for Pulmonology and Thoracic Surgery
  • Donaustauf, Germany, 93093
    • Klinik Donaustauf-Zentrum für Pneumologie
  • Essen, Germany, 45239
    • Ruhrlandklinik, Pneumologie/Allergologie
  • Freiburg, Germany, 79106
    • Medizinische Universitätsklinik, Abteilung Pneumologie
  • Giessen, Germany, 35392
    • Justus-Liebig-Universitat Giessen-Zentrum für Innere Medizin
  • Heidelberg, Germany, 01640
    • Thoraxklinik Heidelberg GmbH
  • Immenhausen, Germany
    • Fachklinik für Lungenerkrankungen
  • Löwenstein, Germany, 74245
    • Klinik Löwenstein GmbH-Medizinische Klinik 1 Pneumologie-Kardiologie
  • Munich, Germany, 81377
    • Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Grosshadern
• Ireland
  • Dublin 7, Ireland
    • Mater Misicordiae Hospital
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Centre-Div. for Pulmonary Disease
  • Jerusalem, Israel, 91120
    • Hadassah Medical Organization: Ein Karem-Institute of Pulmonology
  • Petach Tikvah, Israel
    • Pulmonary Istitute-Rabin Medical Centre: Beilinson Campus
  • Rehovot, Israel, 76100
    • Kaplan Medical Centre-Pulmoary Istitute
  • Tel-Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Centre-Institute of Pulmonary & Allergic Diseases
  • Tel-Hashomer, Israel, 52621
    • Chaim Sheba Medical Centre
• Italy
  • Forli, Italy, 47100
    • Azienda Sanitaria di Forli-Presidio Ospedaliero Stabilimento
  • Milan, Italy, 20123
    • Ospedale San Giuseppe Milanocuore, Unita Operativa di Pneumologia
  • Orbassano (Torino), Italy, 10043
    • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova - Immunologia Clinica
  • Palermo, Italy, 90127
    • Pneumologia ISMETT
  • Siena, Italy, 53100
    • University degli Studi Siena, Policlinico le Scotte
• Japan
  • Aichi
    • Seto, Aichi, Japan, 489-8642
      • Tosei General Hospital
  • Hyogo
    • Himeji, Hyogo, Japan, 670-8520
      • Himeji Medical Center
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular Respiratory Center
  • Nara
    • Tenri, Nara, Japan, 632-8552
      • Tenri Hospital
  • Osaka
    • Sakai, Osaka, Japan, 591-8555
      • Kinki - Chuo Chest Medical Center
• Korea, Republic of
  • Incheon, Korea, Republic of, 405-760
    • Gil Medical Centre, Gachon University
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Centre
  • Seoul, Korea, Republic of, 420-767
    • Soonchunhyang University Bucheon Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum Amsterdam
• Serbia
  • Belgrade, Serbia, 11000
    • Institut za Plucne bolest l TBC Klinickog Centra Srbije
  • Sremska Kamenica, Serbia, 21204
    • Institut za Plucne bolesti Vojvodine, Sremska Kamenica
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona (Pneumology Service)
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron-Neumologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28006
    • Hospital La Princesa
  • Valencia, Spain, 46014
    • Hospital General de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel-Div of Pneumology
  • Bern, Switzerland, 3010
    • Inselspital Bern-Div of Pulmonary Medicine
  • Zurich, Switzerland, 8091
    • University Hopital Zurich-Clinic for Pneumology & Lung Transplant Program
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB23 3RE
    • Papworth Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9LT
    • NWLC, Wythenshawe Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Division of Pulmonary
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90033
      • USC University Hospital
    • Los Angeles, California, United States, 90095
      • UCLA-Division of Pulmonary & Critical Care
    • Sacramento, California, United States, 95817
      • UC Davis University of California
    • San Diego, California, United States, 92103
      • UCSD Medical Center
    • San Francisco, California, United States, 94143
      • UCSF-Interstitial Lung Disease Center
    • Stanford, California, United States, 94305
      • Pulmonary and Critical Care Medicine-Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical & Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine-Dept of Internal Med-Pulmonary & Critical Care
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago - Section of Pulmonary, Dept of Medicine, Respiratory Clinical Research
  • Kansas
    • Olathe, Kansas, United States, 66061
      • Consultants in Pulmonary Medicine
    • Wichita, Kansas, United States, 67208
      • Wichita Clinic, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Medical Group, Cardio-Pulmonary Research
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Pulmonary & Allergy Associates, P.A.
  • New York
    • New York, New York, United States, 10029-6574
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14620
      • Highland Hospital - Pulmonary Department
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5735
      • Vanderbilt Medical Center - IPF Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas-Southwestern Dallas-Div. of Pulm & Critical Care Unit
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia - Div. of Pulmonary & Critical Care
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-3240
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Male or female aged 18 years or older (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception.)
• Proven diagnosis of IPF according to American Thoracic Society / European Respiratory Society (ATS-ERS) statement, of <3 years, with surgical lung biopsy (SLB)

Exclusion Criteria:

• Interstitial lung disease due to conditions other than IPF.
• Presence of extensive honeycombing (HC) on baseline high-resolution computed tomography (HRCT) scan.
• Severe concomitant illness limiting life expectancy (<1 year).
• Severe restrictive lung disease.
• Obstructive lung disease.
• Diffusing capacity of the lung for carbon monoxide <30% predicted.
• Residual volume > or = 120% predicted.
• Documented sustained improvement of patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy.
• Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization).
• Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements.
• Chronic heart failure with New York Heart Association (NYHA) class III/IV or known left ventricular ejection fraction <25%.
• Alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) > 1.5 times the upper limit of the normal ranges.
• Moderate to severe hepatic impairment.
• Serum creatinine > or = 2.5 mg/dl or chronic dialysis.
• Hemoglobin concentration <75% the lower limit of the normal ranges.
• Systolic blood pressure <85 mmHg.
• Pregnancy or breast-feeding.
• Current drug or alcohol dependence.
• Chronic treatment with the following drugs prescribed for IPF (within 4 weeks of randomization):oral corticosteroids (>20 mg/day of prednisone or equivalent), immunosuppressive or cytotoxic drugs, antifibrotic drugs, chronic use of N-acetylcysteine (prescribed for IPF).
• Oral anticoagulants other than those indicated for a venous or arterial thrombotic disease.
• Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) up to 1 week prior to randomization.
• Treatment with an endothelin receptor antagonist up to 3 months prior to randomization.
• Participation in the BUILD 1 trial.
• Treatment with another investigational drug up to 3 months prior to randomization or planned treatment.
• Known hypersensitivity to bosentan or any of the excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosentan; Subjects receive bosentan 62.5 mg twice daily (b.i.d.) for 4 weeks followed by bosentan 125 mg b.i.d (if body weight > 40 kg) or bosentan 62.5 mg b.i.d. (if body weight < 40 kg)	Drug: Bosentan; Bosentan 62.5 mg tablets twice daily (b.i.d.) for 4 weeks followed by bosentan 125 mg tablets b.i.d (if body weight > 40 kg) or bosentan 62.5 mg tablets b.i.d. (if body weight < 40 kg); Other Names: ACT-050088; Ro 47-0203
Placebo Comparator: Placebo; Subjects receive placebo matching the bosentan treatment regimen	Drug: Placebo; Placebo matching bosentan 62.5 mg tablets and 125 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Occurrence of Disease Worsening or Death up to End of Study.	Disease worsening was defined as an event of worsening of pulmonary function tests (PFT) or acute exacerbation of idiopathic pulmonary fibrosis (IPF).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Experienced Either Disease Worsening or Death at 1 Year.	Disease worsening was defined as an event of worsening of pulmonary function tests (PFT) or acute exacerbation of idiopathic pulmonary fibrosis (IPF).	12 months

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Isabelle Leconte, Actelion

Publications and helpful links

General Publications

• King TE Jr, Brown KK, Raghu G, du Bois RM, Lynch DA, Martinez F, Valeyre D, Leconte I, Morganti A, Roux S, Behr J. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Jul 1;184(1):92-9. doi: 10.1164/rccm.201011-1874OC. Epub 2011 Apr 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: October 20, 2006
• First Submitted That Met QC Criteria: October 20, 2006
• First Posted (Estimate): October 24, 2006

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 9, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease; bosentan; Tracleer; Actelion; BUILD 3
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: AC-052-321