Abstract
Background: The efficacy, pharmacokinetics, safety, and tolerability of bosentan (Tracleer® 32 mg, new dispersible tablet for pediatric use) for pulmonary arterial hypertension (PAH) were investigated in Japanese children.
Methods: This was an open-label, multi-center, phase III, single-arm trial. Patients aged ＜15 years with PAH were administered a new pediatric formulation of bosentan (2 mg/kg twice per day). The efficacy of bosentan was evaluated during the first 12 weeks of the trial, and the subsequent period, including a post-marketing study, was evaluated by following a separate protocol. The primary outcome measure was a change in the pulmonary vascular resistance index (PVRI) from baseline to 12 weeks after starting treatment. Secondary outcome measures were changes in World Health Organization functional class (WHO-FC) every 12 weeks. Additionally, the pharmacokinetics of bosentan were evaluated by measuring blood concentrations, area under the curve (AUC), and time-to-peak blood concentrations (Tmax). To assess safety and tolerability, adverse events were evaluated, including those leading to study drug discontinuation.
Results: In total, 6 subjects with a median age of 5.5 years (range, 1–13 years; 4 males, 2 females) were enrolled. The mean change±standard deviation from baseline to Week 12 in PVRI was 4.0±258.6 dyn·sec·m2/cm5, which indicated no significant change in PVRI relative to the baseline value. WHO-FC II was unchanged in all patients. The geometric mean Cmax of bosentan and AUCtau were 494 ng/mL and 2300 ng·h/mL, respectively. Safety and tolerability were satisfactory.
Conclusion: A new pediatric formulation of bosentan was confirmed to be safe and well-tolerated in Japanese children with PAH. There was no worsening in the mean PVRI and WHO-FC.
