Population Pharmacokinetics of Elexacaftor-tezacaftor-ivacaftor in a Paediatric Population
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Area Under the Concentration Time Curve between two administrations of Elexacaftor, Ivacaftor and Tezacaftor
研究概览
简要总结
Cystic fibrosis is a rare, progressive genetic disease caused by a mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Respiratory and nutritional effects are crucial to patients' prognosis. Since the early years of 2010, etiological treatment has been based on the use of CFTRm (CFTR modulator), which aim to restore the function of the mutated protein. Initially used as monotherapy and targeting a limited number of patients, CFTRm has gradually been extended to a larger number of patients, to the point where it now concerns 9 out of 10 patients, through the use of triple therapy with Elexacaftor-Tezacaftor-Ivacaftro (ETI) or Kaftrio(R).
The efficacy of triple therapy is spectacular, revolutionizing the prognosis of the disease. However, the potential for neuropsychological side-effects (20-50% depending on age, but more frequent in young children under 5) and hepatic side-effects (hepatic cytolysis) must be taken into account. A better understanding of pharmacokinetic variability in children, as well as the relationship between exposure to therapeutic effects and adverse reactions, is therefore particularly important.
The aim of this study is to measure the association between the pharmacokinetic parameters of Elexacaftor, Tezacaftor and Ivacaftor (plasma clearance and volume of distribution) and therapeutic or adverse effects in pediatric patients with cystic fibrosis treated with the combination.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 2 to 17 years old
- •Having Cystic Fibrosis
- •Treated by Elexacaftor/Tezacaftor and Ivacaftor (Trikafta® or Kaftrio®)
排除标准
- •Allergy to previous CFTR modulator association (Ivacaftor, lumacaftor)
- •Pregnant women
- •Patient already enrolled in another study with CYP3A4 inhibitor
- •Pulmonary transplant recipient
研究组 & 干预措施
Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics
干预措施: There is no intervention as this is a prospective pharmacokinetics study. (Other)
结局指标
主要结局
Area Under the Concentration Time Curve between two administrations of Elexacaftor, Ivacaftor and Tezacaftor
时间窗: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Area under the concentration time curve between two administrations of (AUC0-tz) of Elexacaftor, Ivacaftor and Tezacaftor
Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor
时间窗: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Measure residual concentration of Elexacaftor, Ivacaftor and Tezacaftor
Maximum Plasma Concentration [Cmax]
时间窗: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
Measured Cmax of Elexacaftor, Ivacaftor and Tezacaftor
次要结局
- Number (Proportion) of Subjects with adverse events(5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing)
- Relationship between Pharmacokinetics/Toxixodynamic and Cystic Fibrosis mutational status(5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing)
- Area Under the Effect Time curve (AUEC) of Sweat Chloride(5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing)
- Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations(5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing)
- Relationship between Pharmacokinetics and Cystic Fibrosis mutational status and Adverse Event(5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing)