BUILD 3: Bosentan Use in Interstitial Lung Disease

Idiopathic Pulmonary Fibrosis Clinical Trial

— BUILD 3  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00391443
• Other study ID #: AC-052-321
• Status: Completed
• Phase: Phase 3
• First received: October 20, 2006
• Last updated: September 9, 2015
• Start date: February 2007
• Est. completion date: July 2010

Study information

• Verified date: August 2015
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 616
• Est. completion date: July 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

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)
• Placebo
Placebo matching bosentan 62.5 mg tablets and 125 mg tablets

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital-Respiratory Clinical Trials Unit	Adelaide	South Australia
Australia	Prince Charles Hospital - Lung Transplant, Thoraic Dept.	Chermside	Queensland
Australia	St. Vincent's Public Hospital, Lung Transplantation & Respiratory Medicine	Darlinghurst	New South Wales
Australia	Royal Perth Hospital; Advanced Lung Disease Unit	Perth	Western Australia
Austria	Medizinische Universität Graz-Klinische Abteilung für Pulmonologie	Graz
Austria	Landesklinikum Thermenregion Hochegg	Grimmenstein
Austria	Medical University of Innsbruck-Div. of Clinical & Internal Medicine	Innsbruck
Austria	Medical University of Vienna and AKH-Div of Pulmonology	Wien
Austria	Otto-Wagner Spital Wien	Wien
Belgium	UZ Gasthuisberg	Leuven
Canada	Walter C. Mackenzie Health Sciences Centre-Univeristy of Alberta	Edmonton	Alberta
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Lawson Health Research Institute	London	Ontario
Canada	Hopital Notre Dame - Centre Hospitalier de L'Universit de Montreal	Montreal	Quebec
Canada	The Health Care Corporation of St. John's-Eastern Health	St. John's	Newfoundland and Labrador
Canada	Institut de Cardiologie et de Pneumologie de l'Universite Laval	Ste-Foy	Quebec
Canada	Toronto General Hospital-Rosedale Medical Center PFT Lab	Toronto	Ontario
Croatia	University Hospital for Lung Disease "Jordanovac"	Zagreb
Czech Republic	University Hospital Olomouc - Dept of Respiratory Disease-IP Pavlova	Olomouc
Czech Republic	Thomayer Faculty Hospital Prague-Dept of Respiratory Disease	Praha 4
Czech Republic	University Hospital Na Bulovce	Praha 8
France	Hopital Avicenne	Bobigny
France	Hopital Louis Pradel	Bron
France	HYLAB, Clinique du Mail	Grenoble
France	CHRU de Lille-Hopital Albert Calmette	Lille Cedex
France	CHU Hôpital Arnaud de Villeneuve	Montpellier
France	Hôpital Bichat	Paris
Germany	HELIOS Klinikum Emil von Behring	Berlin
Germany	Fachkrankenhaus Coswig; Centre for Pulmonology and Thoracic Surgery	Coswig
Germany	Klinik Donaustauf-Zentrum für Pneumologie	Donaustauf
Germany	Ruhrlandklinik, Pneumologie/Allergologie	Essen
Germany	Medizinische Universitätsklinik, Abteilung Pneumologie	Freiburg
Germany	Justus-Liebig-Universitat Giessen-Zentrum für Innere Medizin	Giessen
Germany	Thoraxklinik Heidelberg GmbH	Heidelberg
Germany	Fachklinik fur Lungenerkrankungen	Immenhausen
Germany	Klinik Löwenstein GmbH-Medizinische Klinik 1 Pneumologie-Kardiologie	Löwenstein
Germany	Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Grosshadern	Munich
Ireland	Mater Misicordiae Hospital	Dublin 7
Israel	Rambam Medical Centre-Div. for Pulmonary Disease	Haifa
Israel	Hadassah Medical Organization: Ein Karem-Institute of Pulmonology	Jerusalem
Israel	Pulmonary Istitute-Rabin Medical Centre: Beilinson Campus	Petach Tikvah
Israel	Kaplan Medical Centre-Pulmoary Istitute	Rehovot
Israel	Tel-Aviv Sourasky Medical Centre-Institute of Pulmonary & Allergic Diseases	Tel-Aviv
Israel	Chaim Sheba Medical Centre	Tel-Hashomer
Italy	Azienda Sanitaria di Forli-Presidio Ospedaliero Stabilimento	Forli
Italy	Ospedale San Giuseppe Milanocuore, Unita Operativa di Pneumologia	Milan
Italy	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano (Torino)
Italy	Azienda Ospedaliera di Padova - Immunologia Clinica	Padova
Italy	Pneumologia ISMETT	Palermo
Italy	University degli Studi Siena, Policlinico le Scotte	Siena
Japan	Himeji medical center	Himeji	Hyogo
Japan	Kinki - Chuo Chest Medical Center	Sakai	Osaka
Japan	Tosei General Hospital	Seto	Aichi
Japan	Tenri Hospital	Tenri	Nara
Japan	Kanagawa Cardiovascular Respiratory Center	Yokohama	Kanagawa
Korea, Republic of	Gil Medical Centre, Gachon University	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Centre	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	SoonChunHyang University Bucheon Hospital	Seoul
Netherlands	Academisch Medisch Centrum Amsterdam	Amsterdam
Serbia	Institut za Plucne bolest l TBC Klinickog Centra Srbije	Belgrade
Serbia	Institut za Plucne bolesti Vojvodine, Sremska Kamenica	Sremska Kamenica
Spain	Hospital Clinic Barcelona (Pneumology Service)	Barcelona
Spain	Hospital Vall d'Hebron-Neumologia	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital General de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Switzerland	University Hospital Basel-Div of Pneumology	Basel
Switzerland	Inselspital Bern-Div of Pulmonary Medicine	Bern
Switzerland	University Hopital Zurich-Clinic for Pneumology & Lung Transplant Program	Zurich
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Royal Brompton Hospital	London
United Kingdom	NWLC, Wythenshawe Hospital	Manchester
United States	Emory University	Atlanta	Georgia
United States	UAB Division of Pulmonary	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston University School of Medicine	Boston	Massachusetts
United States	PAB Clinical Research	Brandon	Florida
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia - Div. of Pulmonary & Critical Care	Charlottesville	Virginia
United States	St. Luke's Medical Group, Cardio-Pulmonary Research	Chesterfield	Missouri
United States	University of Chicago - Section of Pulmonary, Dept of Medicine, Respiratory Clinical Research	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Vermont Lung Center	Colchester	Vermont
United States	University of Texas-Southwestern Dallas-Div. of Pulm & Critical Care Unit	Dallas	Texas
United States	National Jewish Medical & Research Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Heart and Vascular Institute	Falls Church	Virginia
United States	Baylor College of Medicine	Houston	Texas
United States	UCLA-Division of Pulmonary & Critical Care	Los Angeles	California
United States	USC University Hospital	Los Angeles	California
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Medical Center - IPF Center	Nashville	Tennessee
United States	Yale University School of Medicine-Dept of Internal Med-Pulmonary & Critical Care	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	Consultants in Pulmonary Medicine	Olathe	Kansas
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Pulmonary Associates	Phoenix	Arizona
United States	Highland Hospital - Pulmonary Department	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis University of California	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	UCSD Medical Center	San Diego	California
United States	UCSF-Interstitial Lung Disease Center	San Francisco	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	Pulmonary and Critical Care Medicine-Stanford University Medical Center	Stanford	California
United States	Pulmonary & Allergy Associates, P.A.	Summit	New Jersey
United States	Wichita Clinic, P.A.	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Croatia,  Czech Republic,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Serbia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No