To evaluate the efficacy, safety, and tolerabilitiy of macitentan in patients with idiopathic pulmonary fibrosis. MedDRA version: 9.1 Level: LLT Classification code 10021240 Term: Idiopathic pulmonary fibrosis
Conditions
Interventions
Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Tablet
INN or Proposed INN: macitentan
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent. 2. Male or female patients of at least 18 years of age (females of child-bearing potential must use a reliable method of contraception). 3. IPF diagnosis within 3 years prior to randomization, proven according to ATS/ERS consensus statement, with surgical lung biopsy. 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
Exclusion criteria: 1. Interstitial lung disease due to conditions other than IPF. 2. Presence of extensive HC on Baseline high-resolution computed tomography (HRCT) scan performed within 3 months prior to randomization. The patient is not allowed in the study if HC involves more than 5% of the parenchyma in 3 or more of the 6 zones (i.e., right and left lung, viewed at the levels of tracheal carina, inferior pulmonary veins, and 1 cm above the dome of the diaphragm), whether the involvement is unilateral or bilateral. 3. Severe concomitant illness limiting life expectancy ( 1.5 × ULN. 15. Hemoglobin 20 mg/day of prednisone or equivalent), • Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine, • Antifibrotic drugs including pirfenidone, D-penicillamine, colchicine, TNFa blocker, imatinib, interferon ?, • Chronic use of N-acetylcysteine > 600 mg/day (prescribed for IPF). • Oral anticoagulants prescribed for IPF. 20. Treatment with ERAs within 4 weeks prior to randomization. 21. Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin [mTOR] inhibitors). 22. Treatment with CYP3A inducers within 4 weeks prior to randomization. 23. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients. 24. Planned treatment, or treatment, with another investigational drug within 4 weeks prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary Endpoint Change from baseline to end of Period 1 in Forced Vital Capacity (FVC). A mean difference from placebo of at least 0.1 liter is to be detected. This parameter is expected to be normally distributed with a standard deviation of 0.2 liter. Secondary Endpoint Time to occurrence of disease worsening or death up to EOS. Disease worsening is defined as (i) worsening of PFTs or (ii) acute respiratory decompensation of IPF. (i) Worsening of PFTs (confirmed by two tests at least 4 weeks apart) is defined as the occurrence of both: ? Decrease from baseline = 10% in FVC (absolute values, i.e., liters) and ? Decrease from baseline = 15% in corrected DLCO (absolute values, i.e., ml•mmHg-1•min-1) A patient unable to perform PFTs at a planned visit due to worsening of IPF will be considered as having a worsening of PFTs if this is not invalidated by a test at a follow-up visit. (ii) Acute respiratory decompensation of IPF is defined as: An unexplained rapid deterioration of patient’s condition within 4 weeks with an increasing shortness of breath requiring oxygen supplementation = 5 liters/min to maintain a resting SaO2 = 90% or PaO2 = 55 mmHg (sea level) or 50 mmHg (high altitude). A documented acute respiratory decompensation of IPF will be considered to be an event, irrespective of the results of any follow-up PFTs or fatal outcome. Patients who are transplanted (without a prior documented disease worsening),or who undergo a surgery/procedure that affects lung functions in a long-lasting and irreversible manner, or who withdraw their consent, or those lost to follow-up before the EOS will be censored. Patients starting forbidden IPF medications (without prior documented disease worsening as defined above) will not be considered as having IPF worsening. Exploratory endpoints • Time to death (all causes) up to End-of-Study. • Time to occurrence of disease worsening up to EOS. • Proportion of patients who experienced either disease worsenin | — |
Countries
France, Germany, Italy, Slovenia, Spain, Sweden
Outcome results
None listed