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 hypertension - SERAPHI

Phase 1

• Conditions: To assess the effects of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10064911Term: Pulmonary arterial hypertension

• Registration Number: EUCTR2007-002440-14-BE
• Lead Sponsor: Actelion Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12-18
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

1.Signed informed consent prior to initiation of any study mandated procedure.
2.Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV.
3.Patients with the following types of PAH belonging to groups 1.1 to 1.3 of the Venice classification:
a.Idiopathic (IPAH);
b.Familial (FPAH); or
c.Related to:
i.Collagen vascular disease;
ii.Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;
iii.HIV infection; or
iv.Drugs and toxins.
4.PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following:
a.Mean pulmonary artery pressure (mPAP) >25 mmHg at rest;
b.Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) <= 15 mmHg; and
c.Pulmonary vascular resistance (PVR) at rest >= 320 dyn*sec/cm5.

?For patients who participate in the pharmacokinetic/ pharmacodynamic substudy, hemodynamic evaluation must have been performed within 3 months prior to randomization.
?For all other patients, hemodynamic evaluation must have been performed within 1 year prior to randomization.

5.6-minute walk distance (6MWD) >= 50 m
at screening and randomization
The 6MWT performed at screening and randomization must satisfy the following
requirements:
• 6MWT distance must be > 50 m or patient cannot be included in the study.
• 6MWT #2 (at Randomization) distance should be within 10% of 6MWT #1
distance (at Screening) or a third test is required (6MWT #3).
• 6MWT #3 (at Randomization) distance should be within 10% of 6MWT #2
distance or the patient cannot be included in the study.

6.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).

Are the trial subjects under 18? yes
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
2.PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
3.PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
4.Persistent pulmonary hypertension of the newborn.
5.Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
6.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.
7.Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value.
8.Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
9. Estimated Creatinine clearance <30mL/min
10.Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
11.Hemoglobin < 75% of the lower limit of the normal range.
12.Systolic blood pressure < 100 mmHg.
13.Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
14.Pregnant or breast-feeding.
15.Known concomitant life-threatening disease with a life expectancy < 12 months.
16.Body weight < 40 kg.
17.Any condition that prevents compliance with the protocol or adherence to therapy.
18.Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
19.Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
20.Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).
21. Treatment with CYP3A inducers within 4 weeks prior to randomization.
22.Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
23.Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified