Clinical trial NCT00071461 (phase 2/phase 3, status: completed)
Conditions: idiopathic pulmonary fibrosis
ICD codes: J84.112
Drugs: bosentan, placebo
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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.