Status:
COMPLETED
Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Lead Sponsor:
Actelion
Conditions:
Pulmonary Arterial Hypertension
Eligibility:
All Genders
12+ years
Phase:
PHASE3
Brief Summary
The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of macitentan (ACT-064992) (3 and 10 mg) vs placebo in patients with symptomatic PAH. The main stud...
Eligibility Criteria
Inclusion
- Signed informed consent prior to initiation of any study mandated procedure.
- Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV.
- Patients with the following types of pulmonary arterial hypertension (PAH) belonging to groups 1.1 to 1.3 of the Venice classification:
- Idiopathic (IPAH);
- Familial (FPAH); or
- Related to:
- Collagen vascular disease;
- Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;
- Human immunodeficiency virus (HIV) infection; or
- Drugs and toxins.
- PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following:
- Mean pulmonary artery pressure (mPAP) \> 25 mmHg at rest;
- Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) \< 15 mmHg; and
- Pulmonary vascular resistance (PVR) at rest \>= 320 dyn×sec/cm\^5.
- 6-minute walk distance (6MWD) \>= 50 m.
- Men or women \> 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception).
Exclusion
- PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
- PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
- PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
- Persistent pulmonary hypertension of the newborn.
- Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
- Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 70% and FEV1 \< 65% of predicted value after bronchodilator administration.
- Moderate to severe restrictive lung disease: total lung capacity (TLC) \< 60% of predicted value.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- Estimated creatinine clearance \< 30 mL/min
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal.
- Hemoglobin \< 75% of the lower limit of the normal range.
- Systolic blood pressure \< 100 mmHg.
- Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
- Pregnant or breast-feeding.
- Known concomitant life-threatening disease with a life expectancy \< 12 months.
- Body weight \< 40 kg.
- Any condition that prevents compliance with the protocol or adherence to therapy.
- Recently started (\< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
- Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
- Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors).
- Treatment with cytochrome P3A (CYP3A) inducers within 4 weeks prior to randomization
- Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
- Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
Key Trial Info
Start Date :
May 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2012
Estimated Enrollment :
742 Patients enrolled
Trial Details
Trial ID
NCT00660179
Start Date
May 1 2008
End Date
April 1 2012
Last Update
September 28 2015
Active Locations (153)
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1
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249-0001
2
Arizona Pulmonary Specialists
Pheonix, Arizona, United States, 85013
3
GLVA Healthcare Center
Los Angeles, California, United States
4
University of California, San Diego
San Diego, California, United States