An Open Label, Multicenter Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Pediatric Formulation of Bosentan in Children With Idiopathic or Familial Pulmonary Arterial Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 主要终点
- Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan
研究概览
简要总结
The aim of the study is to demonstrate that the exposure to bosentan in children with idiopathic pulmonary arterial hypertension (PAH) or familial pulmonary arterial hypertension, using a pediatric formulation, is similar to that in adults with PAH and to evaluate the tolerability and safety of a pediatric formulation of bosentan in this patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by the parents or the legal representatives.
- •Males or females >= 2 and < 12 years of age.
- •Idiopathic PAH or familial PAH diagnosed by right heart catheterization (Clinical classification of pulmonary hypertension, Venice 2003).
- •World Health Organization (WHO) functional class II or III.
- •Oxygen saturation (SpO2) >= 88% (at rest, on room air).
- •PAH treatment-naïve patients or patients already treated with either:
- •Bosentan monotherapy
- •Intravenous epoprostenol monotherapy
- •Intravenous or inhaled iloprost monotherapy
- •Combination of bosentan and intravenous epoprostenol
- •Combination of bosentan and intravenous or inhaled iloprost.
- •All patients should start the study drug (bosentan pediatric formulation) at 2 mg/kg twice daily (b.i.d.), whether or not they were previously treated with bosentan.
- •PAH therapy stable for at least 3 months prior to Screening.
- •Stable treatment with calcium channel blockers, if any, for at least 3 months prior to Screening.
- •Patient's PAH condition stable for at least 3 months prior to Screening.
排除标准
- •PAH associated with conditions other than idiopathic or familial PAH.
- •Non-stable patients, e.g., history (in the last 3 months prior to Screening) of recurrent syncope, or signs and symptoms of non-compensated right heart failure.
- •Need or plan to wean patients from intravenous epoprostenol, or intravenous, or inhaled iloprost.
- •Body weight < 4 kg.
- •Systolic blood pressure < 80%, the lower limit of normal range, according to age and gender.
- •AST and/or ALT values > 3 times the upper limit of normal ranges.
- •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- •Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal ranges.
- •Pregnancy.
- •Known intolerance or hypersensitivity to bosentan or any of the excipients.
研究组 & 干预措施
Bosentan
The initial dose of bosentan was 2 mg/kg b.i.d. for 4 weeks. After 4 weeks, the initial dose was up-titrated to the maintenance dose of 4 mg/kg b.i.d. up to the end of the study treatment at Week 12. If the maintenance dose was not well tolerated, the dose could be down-titrated to the initial dose.
干预措施: Bosentan (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan
时间窗: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose
AUCt was assessed at steady state (i.e., after at least 2 weeks of treatment with a same dose of the study drug) over 12 hours .
次要结局
- Time to reach the maximum plasma concentration (tmax) of bosentan and its metabolites(At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose)
- Maximum plasma concentration (Cmax) of bosentan and its metabolites(At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose)
- Area under the plasma concentration-time curve during a dose interval (AUCt) for the metabolites of bosentan(At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose)