Hypertension, Pulmonary
Conditions
Sponsors
Bayer Healthcare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children aged =6 to 240 dyn•sec•cm-5 (i.e., =3.0 wood units•m2) 5. Patients must be treated with standard of care comprising background therapy and stable dose of bosentan (at least 12 weeks with stable doses). Two groups of patients will be included: o Prevalent: Patients currently on monotherapy with bosentan who need additional treatment (discretion of the investigator) o Incident: Treatment naïve patients initiated on bosentan then riociguat added once bosentan dose is stable for at least 12 weeks. 5. WHO functional class I-III 6. Adolescent females of childbearing potential can only be included in the study if a pregnancy test is negative. Adolescent females of childbearing potential must agree to use adequate contraception when sexually active. ‘Adequate contraception’ is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Adequate contraception is required from the signing of the informed consent form up until 6 weeks after the last study drug administration. 7. Young men must agree to use adequate contraception when sexually active. 8. Written inform consent provided and if applicable child assent provided Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Concomitant use of the following medication: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific PDE inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form, or pre-treatment within the last 2-weeks before Visit 1: NO donors (e.g. nitrates) 2. Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening 3. Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004) 4. History of left-sided heart disease, including valvular disease or heart failure 5. Pulmonary hypertension related to conditions other than specified in the inclusion criteria 6. WHO functional class IV 7. Pulmonary veno-occlusive disease 8. Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN) 9. Non-stable disease status, e.g. , signs and symptoms of decompensated right heart failure 10. Severe bronchial asthma 11. Severe restrictive lung disease 12. Severe congenital abnormalities of the lung, thorax, and diaphragm 13. Clinically relevant hepatic dysfunction (especially Child Pugh C) 14. Renal insufficiency (glomerular filtration rate <30 mL/min e.g. calculated based on Cockroft formula) 15. Subject with hypersensitivity to the investigational drug or any of the excipients 16. Active smoking of tobacco of any type or quantity 17. Subjects with known HIV infection (evaluated by medical history) 18. Previous assignment to treatment during this study 19. Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s) 20. Any condition that, according to treating physician, might jeopardize subject's participation and compliance with procedures indicated in this protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate safety, tolerability and pharmacokinetics/pharmacodynamics of bodyweight adjusted riociguat treatment in children with PAH.;Secondary Objective: Secondary exploratory objectives are to characterize the pharmacodynamic profile of riociguat comprising the following exploratory parameters: time to clinical worsening (TTCW), exercise capacity (6MWD test), functional capacity (measured by WHO FC), laboratory biomarkers (NT-proBNP), QoL measurements (SF-10), echocardiographic variables and taste assessment (questionnaire).;Primary end point(s): - Incidence of adverse events and serious adverse events - recording of vital signs - left-hand x-ray Pharmacokinetics/Pharmacodynamics analyses;Timepoint(s) of evaluation of this end point: Assessment of Adverse Events at baseline, at all visits in the titration phase and maintenance phase, and every 3-4 months in the extension phase. Left hand x-ray at baseline, end of study treatment period (week 24) and every 12 months in the extension phase until growth plates are closed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 6-Minute Walking Distance (6MWD). - WHO functional class. - N-terminal prohormone brain-type natriuretic peptide. - Quality of Life scores (parent questionnaire and in children able to understand questions). - Echocardiographic parameters including: o pulmonary arterial systolic pressure (PASP), o tricuspid annular plane systolic excursion (TAPSE), o pericardial effusion, o left ventricular eccentricity index, o estimated inferior vena cava pressure. - Time to clinical worsening defined as: o hospitalization for right heart failure, o death, o lung transplantation, o Pott’s anastomosis and atrioseptostomy o worsening of PAH symptoms, which must include either an increase in WHO functional class, OR both appearance/worsening symptoms of right heart failure AND need for additional PAH therapy. -Taste and texture of the pediatric formulation(s) must be assessed by use of a questionnaire.;Timepoint(s) of evaluation of this end point: Changes from baseline to end of treatment (week 24) | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Romania, Spain, Turkey, United Kingdom
Contacts
Public ContactBayer Clin. Trials Contact CTP Team
Bayer HealthCare AG
Outcome results
None listed