E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive pulmonary sarcoidosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037430 |
E.1.2 | Term | Pulmonary sarcoidosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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. |
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E.2.2 | Secondary objectives of the trial |
• 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |