Hypertension, pulmonary
Conditions
Interventions
investigational material(s)
Generic name etc : Riociguat (Adempas, BAY63-2521)
INN of investigational material : Riociguat
Therapeutic category code : 219 Other cardiovascular agents
Dosage and Admini
Sponsors
Bayer Yakuhin, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Children aged >=6 to =25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) =240 dynseccm-5 (i.e., >=3.0 wood unitsm2) - Patients must be on standard of care PAH medications, allowing Endothelin Receptor Antagonists (ERA) and/or Prostacyclin Analogues (PCA), for at least 12 weeks prior to baseline visit. Two groups of patients will be included: -Prevalent: Patients currently on PAH medication (allowing ERA and/or PCA) who need additional treatment (discretion of the investigator) -Incident: Treatment naive patients initiated on PAH medication (allowing ERA and/or PCA) and then riociguat added once patients are stable on standard of care - WHO functional class I-III - 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. - Young men must agree to use adequate contraception when sexually active. -Written inform consent provided and if applicable child assent provided
Exclusion criteria
Exclusion criteria: - Concomitant use of the following medications: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form - Pretreatment with NO donors (e.g. nitrates) within the last 2-weeks before visit 1 - 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 - Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004) - History of left-sided heart disease, including valvular disease or heart failure - Pulmonary hypertension related to conditions other than specified in the inclusion criteria - Pulmonary veno-occlusive disease - Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN) - Severe restrictive lung disease - Severe congenital abnormalities of the lung, thorax, and diaphragm - Clinically relevant hepatic dysfunction (especially Child Pugh C) - Renal insufficiency (glomerular filtration rate <35 mL/min e.g. calculated based on Cockroft formula) - PH associated with idiopathic interstitial pneumonia (PH-IIP)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety pharmacokinetics Change in incidence of treatment-emergent adverse events Change in incidence of treatment-emergent serious adverse events Change in heart rate Change in blood pressure Change in bone age x-ray of left hand Plasma concentration of riociguat Baseline to week 24 Day 0, Day 1 (0.5, 1.5 and 2.5h), Day 28, Day 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Change in 6-Minute Walking Distance (6MWD) Change in WHO functional class Change in NT-proBNP (N-terminal pro-brain natriuretic peptide) Changes in echocardiograph from baseline Time to clinical worsening Change in Quality of Life scores as assessed by patient questionnaire and PedsQL generic score Questionnaire to assess both taste and texture of pediatric formulation(s) Baseline to week 24 | — |
Countries
Asia except Japan, Europe, Japan, North America, South America
Contacts
Public Contactcontact Dedicated
Bayer Yakuhin, Ltd.
Outcome results
None listed