Portopulmonary hypertension MedDRA version: 20.0 Level: PT Classification code 10067281 Term: Portopulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
ACTELION Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female 18 years of age with symptomatic PoPH: Documented diagnosis of portal hypertension PAH by right-heart catheterization at screening - Mean pulmonary arterial pressure (mPAP) = 25 mmHg - Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) = 15 mmHg 2) Pulmonary vascular resistance (PVR) = 4 Wood Units or = 320 dyn.s.cm-5 at screening 3) 6MWD = 50 m at screening 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 74 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Severe hepatic impairment, as defined by Child-Pugh Class C liver disease or MELD score = 19 2. Systolic blood pressure (SBP) < 90 mmHg at Screening 3. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 3 X the upper limit of the normal range (ULN) at Screening 4. Bilirubin = 3 mg/dL at Screening 5. Grades 2, 3, or 4 hepatic encephalopathy 6. History of liver transplantation 7. Gastrointestinal bleeding or esophageal varices bleeding < 3 months prior to randomization 8. Treatment with calcium channel blockers, and endothelin receptor antagonist (ERA), i.v./s.c. or oral prostanoids within 3 months prior to randomization 9. Treatment with interferon within 3 months prior to randomization 10. Treatment with strong cytochrome P450 (CYP) 3A4 inducers within 4 weeks prior to randomization 11. Treatment with strong CYP3A4 inhibitors within 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of macitentan on pulmonary vascular resistance (PVR) as compared to placebo in patients with portopulmonary hypertension;Secondary Objective: - To evaluate the effect of macitentan as compared to placebo on cardio-pulmonary hemodynamics, hepatic portal vein pressure, disease severity, and exercise capacity in patients with PoPH. - To evaluate the safety and tolerability of macitentan as compared to placebo in patients with PoPH - To evaluate the pharmacokinetics (PK) of macitentan and its active metabolite ACT-132577 in subjects with PoPH ;Primary end point(s): Primary efficacy endpoint Relative change from Baseline to Week 12 in PVR. ;Timepoint(s) of evaluation of this end point: Screening, Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints • Change from Baseline to Week 12 in mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), total pulmonary resistance (TPR), and mixed venous oxygen saturation (SVO2), all measured at rest • Change from Baseline to Week 12 in 6-minute walk distance (6MWD) • Change from Baseline to Week 12 in WHO functional class • Change from Baseline to Week 12 in NT-proBNP Other efficacy endpoints • Change from Baseline to Week 12 in hepatic venous pressure gradient (HVPG) • Change from Baseline to Week 12 in Borg dyspnea index;Timepoint(s) of evaluation of this end point: - Mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), total pulmonary resistance (TPR), and mixed venous oxygen saturation (SVO2), all measured at rest: Screening, Day 1, Week 12 - 6-minute walk distance (6MWD): Screening, Day 1, Week 4/8, Week 12 - WHO functional class: Screening, Day 1, Week 4/8, Week 12 - NT-proBNP: Screening, Day 1, Week 12 -Hepatic venous pressure gradient (HVPG): Screening, Week 12 - Borg dyspnea index: Screening, Day 1, Week 4/8, Week 12 | — |
Countries
Brazil, Czech Republic, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Medical Information
ACTELION Pharmaceuticals Ltd.
Outcome results
None listed