BUILD 3: Bosentan Use in Interstitial Lung Disease
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: Bosentan; Placebo
Intervention description: 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 matching bosentan 62.5 mg tablets and 125 mg tablets
Intervention MeSH terms: Bosentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 616.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BUILD 3; Idiopathic Pulmonary Fibrosis; Tracleer; Interstitial Lung Disease; bosentan; Actelion

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.
    

Eligibility criteria:

        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.