BUILD 3: Bosentan Use in Interstitial Lung Disease

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.

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.