A multicenter, double-blind, randomized, placebo-controlled, parallel group, event-driven, Phase III study to assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertensio

Not Applicable

• Conditions: I270; -I270 Primary pulmonary hypertension; Primary pulmonary hypertension

• Registration Number: PER-057-08
• Lead Sponsor: Actelion Pharmaceuticals Ltd,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-08-04
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Signed informed consent before initiating any procedure specific to the study.
• Patients with symptomatic pulmonary arterial hypertension (PAH) in modified functional classes II to IV of WHO.
• Patients with the following types of PAH: Idiopathic (IPAH); Family (FPAH)
• The diagnosis of PAH confirmed by hemodynamic evaluation performed before randomization
• Walking distance of 6 minutes (6MWD)> 50 m and <475 m.
• Men or women> 12 years of age (women with pregnancy potential should have a negative pregnancy test before starting treatment and should use a reliable contraceptive method).

Exclusion Criteria

• PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher´s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy.
• PAH associated with simple congenital systemic to pulmonary uncorrected shunts, and combined and complex systemic to pulmonary shunts, corrected or uncorrected.
• PAH associated with significant venous or capillary involvement (PCWP> 15 mmHg), known pulmonary veno-occlusive disease and capillary pulmonary hemangiomatosis.
• Persistent pulmonary hypertension in the newborn.
• Pulmonary arterial hypertension of groups 2 to 5 of the Venice classification.
• Moderate to severe obstructive pulmonary disease: volume volume in first second / forced vital capacity (FEV1 / FVC) <
• 70% and FEV1 <65% of the predicted value after the administration of a bronchodilator.
• Moderate to severe restrictive pulmonary disease: total lung capacity (TLC) <60% of the predicted value.
• Moderate to severe renal insufficiency, ie. Child-Pugh Classification B or C.
• Serum aspartate aminotransferase (AST) and / or alaninaminotransferase (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), which limits the ability to meet the requirements of the study.
• Pregnant or lactating women.
• Concomitant disease that puts life expectancy at risk <12 months.
• Body weight <40 kg.
• Any condition that avoids adherence to the protocol or therapy.
• Cardiopulmonary rehabilitation program based on the recently initiated or planned short-term exercise (<8 weeks before randomization).
• Treatment with endothelin receptor antagonists (ERAs) in the 3 months prior to randomization.
• Systemic treatment in the week prior to randomization with cyclosporin A or tacrolimus, everolimus, sirolimus (calcineurin inhibitors or mTOR inhibitors).
• Known hypersensitivity to drugs of the same class as the study drug, or to any of its excipients.
• Treatment planned, or in progress, with another investigational drug in the month prior to randomization.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:Defined as follows: Death, Atrial septostomy, Lung transplantation, Start of intravenous or subcutaneous prostanoids (e.g., epoprostenol, treprostinil), another worsening of pulmonary arterial hypertension.<br>Measure:Time from the start of treatment to the first event of morbidity or mortality<br>Timepoints:After treatment<br>