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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-005117-18-AT
• Date of registration: 04/03/2008
• Prospective Registration: Yes
• Primary sponsor: Medical University of Vienna, Department of Clinical Pharmacology
• Public title: Safety and efficacy study of bosentan in progressive pulmonary sarcoidosis - BOPSAC
• Scientific title: Safety and efficacy study of bosentan in progressive pulmonary sarcoidosis - BOPSAC
• Date of first enrolment: 03/04/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005117-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria

Key inclusion & exclusion criteria

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Progressive pulmonary sarcoidosis
MedDRA version: 9.1 Level: PT Classification code 10037430 Term: Pulmonary sarcoidosis

Intervention(s)

Trade Name: Tracleer
Product Name: Bosentan
Pharmaceutical Form: Coated tablet
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.
• To asses effect of bosentan treatment on quality of live
• To assess differences in treatment efficacy in patients with and without pulmonary hypertension secondary to pulmonary sarcoidosis

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:
• Pulmonary function test (FVC and DLCO)
• Blood gas analysis (AaDO2)
• HRCT (Oberstein score)
• Cardiopulmonary exercise testing (VO2max)
• Dyspnoea (ATS dyspnea scale)

Secondary ID(s)

640