Status:
COMPLETED
Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis
Lead Sponsor:
Actelion
Conditions:
Idiopathic Pulmonary Fibrosis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
PHASE3
Brief Summary
Endothelin-1 (ET-1) is expressed in a variety of pulmonary pathological conditions including pulmonary vascular disease and pulmonary fibrosis. Bosentan (an oral dual ET-1 receptor antagonist) could ...
Eligibility Criteria
Inclusion
- 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.
- IPF proven diagnosis \< 3 years documented according to ATS/ERS international multidisciplinary consensus, with or without surgical (thoracoscopic or open) chest lung biopsy
- Duration of illness ≥ 3 months.
- Six-minute walk test distance (limited by dyspnea) ≥ 150 meters and \< 500 meters
- Patients who have signed the informed consent form prior to initiation of any study procedure.
Exclusion
- 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.
- History of clinically significant environmental exposure known to cause pulmonary fibrosis (drugs, asbestos, beryllium, radiation, domestic birds, etc.).
- Severe concomitant illness limiting life expectancy (\< 1 year).
- FVC ≥ 90% predicted.
- Severe restrictive lung disease: FVC \< 50% predicted or FVC \< 1.2 l, or DLco \< 30% predicted or residual volume ≥ 120% predicted.
- Severe obstructive lung disease: FEV1/FVC\< 0.65.
- 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).
- Recent pulmonary or upper respiratory track infection (within 4 weeks of randomization).
- PaO2 \< 55 mm Hg (sea level) or 50 mm Hg (altitude) at rest on room air.
- 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.
- Severe chronic heart failure, e.g., NYHA class III or IV and/or left ventricular ejection fraction \< 25%.
- 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).
- Baseline values of liver transaminases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) \> 3 times the upper limit of normal ranges.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- Serum creatinine ≥ 2.5 mg/dl (221 mmol/l) or dialysis.
- Hemoglobin concentration \< 75% the lower limit of normal ranges.
- Systolic blood pressure \< 85 mm Hg.
- Pregnancy or breast-feeding.
- Current drug or alcohol dependence.
- Smoker (≥ 5 cigarettes per day) or former smoker (≥ 5 cigarettes per day) having stopped less than 6 months prior to randomization.
- Recently started (\< 8 weeks from Screening visit) or planned cardio-pulmonary rehabilitation program based on exercise.
- 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.
- Treatment with glibenclamide (glyburide), cyclosporine A or tacrolimus within 1 weeks of randomization.
- Treatment with an endothelin receptor antagonist within 3 months of randomization.
- Treatment within 3 months of randomization or planned treatment with another investigational drug.
- Known hypersensitivity to bosentan or any of the excipients.
Key Trial Info
Start Date :
August 1 2003
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 1 2010
Estimated Enrollment :
158 Patients enrolled
Trial Details
Trial ID
NCT00071461
Start Date
August 1 2003
End Date
May 1 2010
Last Update
February 24 2012
Active Locations (29)
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1
University of Alabama at Birmingham - Pulmonary Division
Birmingham, Alabama, United States, 35294
2
David Geffen School of Medicine at UCLA - Division of Pulmonary and Critical Care Medicine
Los Angeles, California, United States, 90024
3
UCSD Medical Center
San Diego, California, United States, 92103
4
University of California - Ambulatory Care Center
San Francisco, California, United States, 94143