Patients with modified NYHA functional Class II PAH have mild symptoms, but their pulmonary artery pressures are elevated which leads to increased wall stress and silent heart damage progression. Therefore Class I-II patients have a better survival rate than Class III-IV patients (Odds ratio = 1.9) but will eventually deteriorate if untreated. MedDRA version: 9.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension
Conditions
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a)Men or women aged 12 years of age and over (except for countries where this age limit is contrary to specific regulatory requirements). 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. – Reliable method of contraception are: Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide. Intra-uterine devices. Oral, injectable or implantable contraceptives only in combination with a barrier method. – Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception. – Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception. Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile. b) PAH in modified NYHA functional class II due to: 1. PAH idiopathic (Primary Pulmonary Hypertension) 2. PAH secondary to human immunodeficiency virus (HIV) 3. PAH secondary to anorexigens 4. PAH secondary to atrial septum defect (ASD) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) PAH associated with conditions other than those mentioned above, e.g., PAH secondary to portal hypertension, complex congenital heart disease or reverse shunt 2) Severe obstructive lung disease: FEV1/FVC 3 times the upper limit of the normal (ULN) range 11) Hemoglobin concentration < 75% of the lower limit of the normal range 12) Systolic blood pressure (BP) < 85 mmHg 13) Pregnancy or breast-feeding 14) Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise 15) Treatment or planned treatment with another investigational drug within 3 months of randomization. 16) Treatment with an endothelin receptor antagonist or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months of randomization. 17) Treatment for PAH within one month of randomization, excluding calcium channel blockers (if present for at least 1 month before randomization) and anticoagulants. 18) Treatment with calcineurin-inhibitors (e.g., cyclosporine A, tacrolimus), fluconazole, glibenclamide (glyburide) within 1 week of randomization. 19) Known hypersensitivity to bosentan or any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate that bosentan improves exercise capacity and/or cardiac hemodynamics in mildly symptomatic PAH patients.;Secondary Objective: The secondary objectives are to demonstrate that bosentan delays time to clinical worsening, and improves dyspnea, modified NYHA functional class, and quality of life, and to demonstrate that bosentan is safe and well tolerated in this patient population.;Primary end point(s): There are two primary efficacy endpoints to be tested independently to assess the superiority of bosentan over placebo on exercise capacity or cardiac hemodynamics in mildly symptomatic PAH patients, namely: Change from baseline to Month 6 in 6MWT distance Change from baseline to Month 6 in PVR at rest. The main analysis of the primary efficacy endpoints is performed on the All-Randomized set for this superiority study. The All-Treated and Per-Protocol sets are used for the supplementary analysis of the primary efficacy endpoints meant to test the robustness of the main results. | — |
Countries
Austria, Czech Republic, Denmark, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed