[Translation] A multicenter, open-label study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of LCZ696 in pediatric patients aged 1 month to < 18 years with heart failure due to systemic left ventricular systolic dysfunction, followed by a 52-week randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of LCZ696 compared with enalapril
主要目的: 第1部分:确定LCZ696治疗儿童HF患者的药代动力学(PK)和药效学(PD)。第2部分:采用整体评级终点来确定LCZ696治疗儿童HF患者是否优于依那普利。次要目的:第1部分:评估LCZ696治疗儿童HF患者的安全性和耐受性。第2部分:确定LCZ696在延迟至类别1或类别2复合事件(例如,死亡、HF恶化)首次发生的时间方面是否优于依那普利。第2部分:确定LCZ696在改善NYHA(纽约心脏病协会)/Ross功能分级方面是否优于依那普利。第2部分:确定LCZ696在改善患者病情严重程度总体印象量表(PGIS)评分方面是否优于依那普利。第2部分:描述儿童HF患者中LCZ696暴露的群体PK特征,包括评估组2患者亚组中的稳态稀疏采样PK数据。第2部分:评估LCZ696相比依那普利治疗儿童HF患者的安全性和耐受性。
[Translation] Primary Objectives: Part 1: Determine the pharmacokinetics (PK) and pharmacodynamics (PD) of LCZ696 in pediatric patients with HF. Part 2: Determine whether LCZ696 is superior to enalapril in the treatment of pediatric patients with HF using an overall rating endpoint. Secondary Objectives: Part 1: Evaluate the safety and tolerability of LCZ696 in pediatric patients with HF. Part 2: Determine whether LCZ696 is superior to enalapril in delaying the time to the first occurrence of a composite of Category 1 or Category 2 event (e.g., death, worsening HF). Part 2: Determine whether LCZ696 is superior to enalapril in improving NYHA (New York Heart Association)/Ross functional class. Part 2: Determine whether LCZ696 is superior to enalapril in improving Patient Global Impression of Severity of Illness Scale (PGIS) scores. Part 2: Characterize the population PK of LCZ696 exposure in pediatric patients with HF, including evaluation of steady-state sparsely sampled PK data in the subgroup of patients in Group 2. Part 2: Evaluate the safety and tolerability of LCZ696 compared to enalapril in the treatment of pediatric patients with HF.