Safety and efficacy study of bosentan in progressive pulmonary sarcoidosis - BOPSAC

• Conditions: Progressive pulmonary sarcoidosis; MedDRA version: 9.1Level: PTClassification code 10037430Term: Pulmonary sarcoidosis

• Registration Number: EUCTR2007-005117-18-AT
• Lead Sponsor: Medical University of Vienna, Department of Clinical Pharmacology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Signed informed consent prior to any study-mandated procedure.
• Male and female patients aged > 18 and < 70 yrs.
• Histologically proven sarcoidosis diagnosed at least one year before screening.
• Diagnosis of sarcoidosis and with evidence of pulmonary parenchymal disease on chest X-ray or CT (radiological stage II, III) with or without pulmonary hypertension. Subjects with concurrent extrapulmonary sarcoidosis are encouraged to be enrolled.
• Progressive disease, defined as follows:
o Deterioration in the 3-12 month period prior to screening in at least two of the
following criteria:
- increase in clinical symptoms (cough, shortness of breath, chest pain,
fatigue or hemoptysis).
- lung function: decrease of 10 % in TLC, FVC or DLCO.
- worsening of radiographic opacities.
o Have been receiving pre-study treatment with prednisolone (or equivalent
dose of corticosteroid) as a single agent (= 10 mg/day) or other
immunosuppressants (methotrexate, azathioprine, cyclophosphamide, TNF
inhibitors, etc.) within the 3-month period immediately prior to screening.
Patients must be on a stable dose of these medicatins for > 4 weeks before
starting the study medication.
• AST and ALT values within three times upper limit of normal.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
• Negative pregnancy test in female patients.
• Adequate contraception in female patients of childbearing age.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Known hypersensitivity to any excipients of the drug formulation or to bosentan.
• Treatment with another investigational drug within 3 months prior to screening.
• Pulmonary sarcoidosis
o without disease progression as defined above
o with radiological stage I
o with radiological stage IV (pulmonary fibrosis with evidence of honey-combing,
hilar retraction, bullae and cysts)
• Other cause of pulmonary disease:
o Active tuberculosis (or positive Quantiferon test), fungi infection, lymphoma.
o Chronic obstructive pulmonary disease, asthma, interstitial lung disease other
than sarcoid-related
• Anamnesis of beryllium or asbestos exposition
• Previous smoking (> 10 PY), or active smoker
• Previous administration of bosentan
• Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
• Positive results from the HIV serology at screening.
• Malignancy requiring chemotherapy or radiation
• Uncontrolled other disease like
o Chronic heart failure (NYHA III, IV)
o Diabetes mellitus (blood glucose 2x per day > 250 mg/dl , HbA1c > 10 %)
o Arterial hypertension (SBP > 180 mmHg)
• Concomitant treatment with cyclosporine A
• Concomitant treatment with tacrolimus or sirolimus
• Concomitant treatment with glibenclamid
• Are pregnant, nursing, or planning pregnancy during the trial or within six month period thereafter
• Have a known substance dependency (drug or alcohol within 3 years of screening)
• Presumed non-compliance.
• Legal incapacity or limited legal capacity at screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To demonstrate treatment efficacy of bosentan as add-on therapy in progressive pulmonary sarcoidosis in comparison to placebo, as measured by a composite clinical score based on pulmonary function test, cardiopulmonary exercise testing, HRCT and dyspnoea level.;Secondary Objective: • To assess safety and tolerability of bosentan in patients with pulmonary sarcoidosis.<br>• To asses effect of bosentan treatment on quality of live<br>• To assess differences in treatment efficacy in patients with and without pulmonary hypertension secondary to pulmonary sarcoidosis<br>;Primary end point(s): Treatment efficacy of bosentan compared to placebo is based on disease progression from screening to EOS investigation assessed by a composite clinical score, including six parameters:<br>• Pulmonary function test (FVC and DLCO)<br>• Blood gas analysis (AaDO2)<br>• HRCT (Oberstein score)<br>• Cardiopulmonary exercise testing (VO2max)<br>• Dyspnoea (ATS dyspnea scale)