BUILD 3: Bosentan Use in Interstitial Lung Disease

Study Overview
=================
Brief 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.

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.

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: Bosentan
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosentan<br>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<br>* 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)<br>* Other names: ACT-050088;|
| Placebo Comparator: Placebo<br>Subjects receive placebo matching the bosentan treatment regimen | Drug: Placebo<br>* Placebo matching bosentan 62.5 mg tablets and 125 mg tablets<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BUILD 3, Idiopathic Pulmonary Fibrosis, Tracleer, Interstitial Lung Disease, bosentan, Actelion