Humberto García Aguilar, Matthias Gorenflo, D. Dunbar Ivy, Shahin Moledina, Biagio Castaldi, Hidekazu Ishida, Paweł Cześniewicz, Jacek Kusa, Oliver Miera, Joseph Pattathu, Ken‐Pen Weng, Laszlo Ablonczy, Christian Apitz, Marta Katona, Kenichi Kurosaki, Tomas Pulido, Hiroyuki Yamagishi, Kazushi Yasuda, Galia Cisternas, Melanie Goth, Susanne Lippert, Anna Radomskyj, Soundos Saleh, Stefan Willmann, Gabriela Wirsching, Damien Bonnet, Maurice Beghetti
Centro Médico Nacional 20 de Noviembre. Heidelberg University Medical Centre. University of Colorado School of Medicine and Children’s Hospital Colorado. Great Ormond Street Hospital for Children. Azienda Ospedaliera di Padova. Osaka University Graduate School of Medicine. Regional Specialist Hospital Research and Development Center. German Heart Center. Kaohsiung Veterans General Hospital. Hungarian Institute of Cardiology. University Children’s Hospital Ulm. Albert Szent-Györgyi Medical Center and University of Szeged. National Cerebral and Cardiovascular Center. Ignacio Chavez National Heart Institute. Keio University Hospital. Aichi Children’s Health and Medical Center. Bayer AG, Pharmaceuticals. Hôpital Necker Enfants malades APHP Université de Paris. University Hospitals of Geneva and Children’s University Hospital University of Geneva and Lausanne.
Multiple Countries
Pulmonary Circulation
Pulm Circ 2022; 12:
DOI: 10.1002/pul2.12133
Abstract
Riociguat, a soluble guanylate cyclase stimulator, is approved for treatment of adults with pulmonary arterial hypertension (PAH). The safety, tolerability, and pharmacokinetics (PK) of oral riociguat in a pediatric population with PAH was assessed in PATENT-CHILD (NCT02562235), a multicenter, single-arm, 24-week, open-label, Phase 3 study. Patients aged 6-17 years in World Health Organization functional class (WHO-FC) I-III treated with stable endothelin receptor antagonists and/or prostacyclin analogs received riociguat equivalent to 0.5-2.5 mg three times daily in adults, as either oral pediatric suspension or tablets, based on bodyweight. Primary outcomes were safety, tolerability, and PK of riociguat. Twenty-four patients (mean age 12.8 years), 18 of whom were in WHO-FC II, were enrolled. Adverse events (AEs), mostly mild or moderate, were reported in 20 patients (83%). Four patients (17%) experienced a serious AE; all resolved by study end and two (8%) were considered study-drug related. Hypotension was reported in three patients and hemoptysis in one (all mild/moderate intensity). Riociguat plasma concentrations in pediatric patients were consistent with those published in adult patients. From baseline to Week 24, mean ± standard deviation increase in 6-minute walking distance was 23 ± 69 m (n = 19), and mean decrease in NT-proBNP was -66 ± 585 pg/ml (n = 14). There was no change in WHO-FC. Two patients experienced clinical worsening events of hospitalization for right heart failure. PK results confirmed a suitable riociguat dosing strategy for pediatric patients with PAH. The data suggest an acceptable safety profile with potential efficacy signals.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Medical Therapy. Pharmacokinetics and Pharmacology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes