Resumen

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 study objective is to demonstrate that macitentan (ACT-064992) prolongs time to the first morbidity or mortality event, and to evaluate the benefit/risk profile of macitentan (ACT-064992) in the treatment of patients with symptomatic PAH.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

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.
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).

Criterios de exclusión

Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
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.
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.

Ubicaciones

Fundacion Favaloro

Buenos Aires, Argentina

Hospital Britanico

Buenos Aires, Argentina

Sanatorio MITRE

Buenos Aires, Argentina

SANATORIO OTAMENDI y MIROLI

Buenos Aires, Argentina

Instituto Cardiologia Corrientes

Corrientes, Argentina

Htal Italiano Cordoba

Córdoba, Argentina

Htla privado de Cordoba

Córdoba, Argentina

'Hospital Italiano - Garibaldi de Rosario

Santa Fe, Argentina

A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

macitentan (ACT-064992)

macitentan (ACT-064992)

placebo

Ubicaciones

Fundacion Favaloro

Hospital Britanico

Sanatorio MITRE

SANATORIO OTAMENDI y MIROLI

Instituto Cardiologia Corrientes

Htal Italiano Cordoba

Htla privado de Cordoba

'Hospital Italiano - Garibaldi de Rosario

Patrocinadores