Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis (BUILD 1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00071461
First received: October 23, 2003
Last updated: February 22, 2012
Last verified: February 2012
  Purpose

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 delay the progression of idiopathic pulmonary fibrosis (IPF), a condition for which no established treatment is available.

The present trial investigates a possible use of bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH) WHO class III and IV, to a new category of patients suffering from IPF.

It was decided to offer Open Label treatment (bosentan) for patients willing to continue in the BUILD 1 study.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: bosentan
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change in 6-minute walk distance [ Time Frame: Baseline to End-of-Period 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Death or treatment failure [ Time Frame: Up to End-of-Period 1 ] [ Designated as safety issue: No ]

Enrollment: 158
Study Start Date: August 2003
Study Completion Date: May 2010
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

Initial dose: 62.5 mg b.i.d. for 4 weeks.

  • Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
  • body weight < 40 kg (90 lb): 62.5 mg b.i.d.
Drug: bosentan

Initial dose: 62.5 mg b.i.d. for 4 weeks.

  • Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
  • body weight < 40 kg (90 lb): 62.5 mg b.i.d.
Other Name: Tracleer
Placebo Comparator: 2

Initial dose: 62.5 mg b.i.d. for 4 weeks.

  • Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
  • body weight < 40 kg (90 lb): 62.5 mg b.i.d.
Drug: Placebo

Initial dose: 62.5 mg b.i.d. for 4 weeks.

  • Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
  • body weight < 40 kg (90 lb): 62.5 mg b.i.d.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071461

  Show 29 Study Locations
Sponsors and Collaborators
Actelion
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00071461     History of Changes
Other Study ID Numbers: AC-052-320, BUILD 1
Study First Received: October 23, 2003
Last Updated: February 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
Idiopathic pulmonary fibrosis
Interstitial lung disease
Bosentan
BUILD

Additional relevant MeSH terms:
Idiopathic Pulmonary Fibrosis
Fibrosis
Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014