Riociguat in children with pulmonary arterial hypertension: The PATENT-CHILD study

Aguilar, Humberto Garcia; Gorenflo, Matthias; Ivy, D. Dunbar; Moledina, Shahin; Castaldi, Biagio; Ishida, Hidekazu; Kusa, Jacek; Miera, Oliver; Pattathu, Joseph; Weng, Ken-Pen; Ablonczy, Laszlo; Apitz, Christian; Katona, Marta; Kurosaki, Kenichi; Pulido, Tomas; Yamagishi, Hiroyuki; Yasuda, Kazushi; Cisternas, Galia; Goth, Melanie; Lippert, Susanne; Radomskyj, Anna; Saleh, Soundos; Willmann, Stefan; Wirsching, Gabriela; Bonnet, Damien; Beghetti, Maurice und Czegniewicz, Pawel (2022): Riociguat in children with pulmonary arterial hypertension: The PATENT-CHILD study. In: Pulmonary Circulation, Bd. 12, Nr. 3, e12133

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2045-8932
• Sprache: Englisch