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Published on: May 11, 2015
Riociguat in children with pulmonary arterial hypertension: The PATENT-CHILD study
Humberto García Aguilar1, Matthias Gorenflo2, D Dunbar Ivy3
1Centro Médico Nacional 20 de Noviembre, ISSSTE Ciudad de México Mexico.
Insights
Riociguat demonstrated an acceptable safety profile in pediatric patients with pulmonary arterial hypertension (PAH). Pharmacokinetics were consistent with adults, supporting its use in children with PAH.
Area of Science:
- Cardiology
- Pediatric Pharmacology
- Pulmonary Hypertension Research
Background:
- Pulmonary arterial hypertension (PAH) is a severe condition affecting adults, with limited treatment options for pediatric patients.
- Riociguat, a soluble guanylate cyclase stimulator, is approved for adult PAH but its pediatric use required evaluation.
- Pediatric PAH necessitates tailored safety and pharmacokinetic assessments for effective treatment.
Purpose of the Study:
- To assess the safety, tolerability, and pharmacokinetics (PK) of oral riociguat in pediatric patients with PAH.
- To establish an appropriate dosing strategy for riociguat in children aged 6-17 years.
- To explore potential efficacy signals of riociguat in the pediatric PAH population.
Main Methods:
- The PATENT-CHILD study (NCT02562235) was a multicenter, single-arm, open-label, Phase 3 trial.
- Twenty-four pediatric patients (aged 6-17 years) with PAH received riociguat based on bodyweight.
- Safety, tolerability, and PK were primary outcomes, with secondary assessments including 6-minute walking distance and NT-proBNP levels.
Main Results:
- Most adverse events (83%) were mild/moderate; serious adverse events occurred in 17% of patients.
- Riociguat plasma concentrations in pediatric patients were comparable to adult levels.
- Improvements in 6-minute walking distance and NT-proBNP levels were observed, alongside two hospitalizations for right heart failure.
Conclusions:
- Riociguat exhibits an acceptable safety profile and suitable pharmacokinetic properties for pediatric PAH treatment.
- The study supports a viable riociguat dosing strategy for children with PAH.
- Potential efficacy signals warrant further investigation in pediatric PAH management.
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.
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