Population Pharmacokinetics of Elexacaftor-tezacaftor-ivacaftor in a Paediatric Population

Condition(s) studied

Investigational drug(s) / intervention(s)

There is no intervention as this is a prospective pharmacokinetics study.: There is no intervention as this is a prospective pharmacokinetics study.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor — 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] — 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing
  Measured Cmax of Elexacaftor, Ivacaftor and Tezacaftor
• Area Under the Concentration Time Curve between two administrations of Elexacaftor, Ivacaftor and Tezacaftor — 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

Trial sites (1)

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