Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00071461
• Date of registration: 23/10/2003
• Prospective Registration: No
• Primary sponsor: Actelion
• Public title: Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis BUILD 1
• Scientific title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Bosentan in Patients With Idiopathic Pulmonary Fibrosis, Open Label Extension
• Date of first enrolment: August 2003
• Target sample size: 158
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00071461
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada, France, Germany, Israel, Italy, Switzerland, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female patients over 18 years of age.

- Women must be either postmenopausal (i.e., amenorrhea for at least 1 year), or
surgically or naturally sterile.

- Women of childbearing potential must have a negative pre-treatment pregnancy
test and use a reliable method of contraception during study treatment and for
at least 3 months after study treatment termination.

2. IPF proven diagnosis < 3 years documented according to ATS/ERS international
multidisciplinary consensus, with or without surgical (thoracoscopic or open) chest
lung biopsy

3. Duration of illness = 3 months.

4. Six-minute walk test distance (limited by dyspnea) = 150 meters and < 500 meters

5. Patients who have signed the informed consent form prior to initiation of any study
procedure.

Exclusion Criteria:

1. Interstitial lung disease due to conditions other than IPF, including but not limited
to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans
with organizing pneumonia, and cancer.

2. History of clinically significant environmental exposure known to cause pulmonary
fibrosis (drugs, asbestos, beryllium, radiation, domestic birds, etc.).

3. Severe concomitant illness limiting life expectancy (< 1 year).

4. FVC = 90% predicted.

5. Severe restrictive lung disease: FVC < 50% predicted or FVC < 1.2 l, or DLco < 30%
predicted or residual volume = 120% predicted.

6. Severe obstructive lung disease: FEV1/FVC< 0.65.

7. Documented improvement of patient's condition within 12 months prior to randomization
with or without IPF-specific therapy (e.g., corticosteroids, immunosuppressive,
cytotoxic or antifibrotic drugs, TNFa blocker, interferon g).

8. Recent pulmonary or upper respiratory track infection (within 4 weeks of
randomization).

9. PaO2 < 55 mm Hg (sea level) or 50 mm Hg (altitude) at rest on room air.

10. Echocardiographic evidence of severe pulmonary hypertension (PH): systolic pulmonary
pressure = 50 mm Hg or tricuspid regurgitation velocity = 3.2 m/sec (unless severe PH
is invalidated by a right heart catheterization). If the pulmonary pressure is not
quantifiable, presence of significant right ventricular enlargement or hypertrophy or
right ventricular dysfunction.

11. Severe chronic heart failure, e.g., NYHA class III or IV and/or left ventricular
ejection fraction < 25%.

12. Acute or chronic impairment (other than dyspnea) limiting the ability to comply with
study requirements, e.g., the 6MWT or the PFTs.

(e.g., angina pectoris, intermittent claudicating, chronic arthritis).

13. Baseline values of liver transaminases, i.e., aspartate aminotransferases (AST)
and/or alanine aminotransferases (ALT) > 3 times the upper limit of normal ranges.

14. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.

15. Serum creatinine = 2.5 mg/dl (221 mmol/l) or dialysis.

16. Hemoglobin concentration < 75% the lower limit of normal ranges.

17. Systolic blood pressure < 85 mm Hg.

18. Pregnancy or breast-feeding.

19. Current drug or alcohol dependence.

20. Smoker (= 5 cigarettes per day) or former smoker (= 5 cigarettes per day) having
stopped less than 6 months prior to randomization.

21. Recently started (< 8 weeks from Screening visit) or planned cardio-pulmonary
rehabilitation program based on exercise.

22. Treatment with oral corticosteroids (> 15 mg/day prednisone or equivalent),
immunosuppressive, cytotoxic or antifibrotic drugs such as TNF alpha blocker, or
interferon gamma within 4 weeks of randomization.within 4 weeks of randomization.

23. Treatment with glibenclamide (glyburide), cyclosporine A or tacrolimus within 1 weeks
of randomization.

24. Treatment with an endothelin receptor antagonist within 3 months of randomization.

25. Treatment within 3 months of randomization or planned treatment with another
investigational drug.

26. Known hypersensitivity to bosentan or any of the excipients.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: bosentan

Drug: Placebo

Primary Outcome(s)

Change in 6-minute walk distance [Time Frame: Baseline to End-of-Period 1]

Secondary Outcome(s)

Death or treatment failure [Time Frame: Up to End-of-Period 1]

Secondary ID(s)

AC-052-320

BUILD 1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors