D

Conditions: Pulmonary Arterial Hypertension (PAH)
MedDRA version: 14.1Level: PTClassification code 10037400Term: Pulmonary hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2010-019883-36-IT

Lead Sponsor: OVARTIS FARMA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 55

Inclusion Criteria

Inclusion criteria Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed 2. Male or female 18 years of age or older who are unable to bear children and females of child bearing potential not disqualified as per Exclusion Criterion 1 (below) 3. WHO Functional Class II or III 4. 6MWD = 150 m and = 450 m at screening. Distances of two consecutive 6MWTs should be within 15% of one another 5. A current diagnosis of Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD or PDA), or PAH associated with diet therapies or other drugs 6. Inadequate clinical response despite stabilization on one or more class(es) of PAH drug [e.g., PDE5 inhibitor, endothelin receptor blocker, vasodilator prostaglandin (systemic, inhaled or oral)] 7. Stabilization of pulmonary hypertension medications defined as observed for = 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: ?? women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner ?? women whose partners have been sterilized by vasectomy or other means ?? using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 10 mIU/mL) 3. History of ventricular tachycardia, ventricular fibrillation or ventricular flutter 4. Use of drugs known to prolong the QT interval or known to be strong CYP3A4 inhibitors (refer to Appendix 6) 5. Untreated or inadequately controlled hypokalemia (<3.5 mmol/L) or hypomagnesemia (<0.65 mmol/L) at the screening visit (Visit 1) 6. Evidence of clinically significant left ventricular dysfunction. 7. Evidence of clinically significant hepatic impairment, including AST or ALT > 3 times the upper limit of normal (if due to bosentan therapy subject is excluded unless bosentan is discontinued and the above LFTs return to < 2 times the upper limit of normal; Subject must still be on a stable regimen including at least one approved PAH therapy at time of study drug randomization). Bilirubin > 2 times the upper limit of normal. [Canada only: AST or ALT > 1.5 times the upper limit of normal] 8. Atrial fibrillation or history of atrial fibrillation in the previous 3 months 9. Having syncope in the 3 months prior to the screening visit 10. History of previous myocardial infarction, unstable angina, or clinically significant bradycardia (<60 bpm and accompanied by clinical symptoms) 11. QRS > 120 ms or > 140 ms in the presence of bundle branch block 12. Current or history of consistently prolonged QTcF (2 or more ECGs in the prior 12 months in the absence of a right bundle branch block or QTcF>450 ms for males and > 470 ms for females at screening); family history of long QT syndrome 13. WHO Class IV 14. History of Torsades de Pointes 15. In treatment with chronic nitric oxide therapy 16. Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, COPD, thorax or diaphragm or bronchial asthma, associated with chronic hypoxia that may contribute to severity of PAH 17. With a pulmonary capillary wedge pressure > 15 mm Hg to rule out PAH secondary to left ventricular dysfunction 18. Diagnosis of pulmonary artery or vein stenosis 19. With other diagnosis of PAH in WHO Diagnostic Group 1 are excluded including congenital systemic to pulmonary shunts (large, small that are not surgically repaired), portal hypertension, HIV infection, glycogen storage disease, Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders) 20. With a diagnosis of PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary t