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NCT Number: NCT07303621

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

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.

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Key information

Conditions

Cystic Fibrosis (CF) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystic Fibrosis Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

2 year–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Children aged 2 to 17 years old
  • Having Cystic Fibrosis
  • Treated by Elexacaftor/Tezacaftor and Ivacaftor (Trikafta® or Kaftrio®)

Exclusion criteria

  • Allergy to previous CFTR modulator association (Ivacaftor, lumacaftor)
  • Pregnant women
  • Patient already enrolled in another study with CYP3A4 inhibitor
  • Pulmonary transplant recipient

Treatment and study plan

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

Other

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

Primary outcomes

  1. Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

    Measure residual concentration of Elexacaftor, Ivacaftor and Tezacaftor

  2. Maximum Plasma Concentration [Cmax]

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

    Measured Cmax of Elexacaftor, Ivacaftor and Tezacaftor

  3. Area Under the Concentration Time Curve between two administrations of Elexacaftor, Ivacaftor and Tezacaftor

    Time frame: 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

Secondary outcomes

  1. Number (Proportion) of Subjects with adverse events

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

    Specific drug related adverse events such as hepatic impairment or neurocomportmental disorder will be monitored.

    All safety data will be analysed using descriptive statistics. Pharmacokinetics analysis will be used to monitor existing relationship between elexacaftor/tezacaftor and ivacaftor

  2. Relationship between Pharmacokinetics and Cystic Fibrosis mutational status and Adverse Event

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

  3. Relationship between Pharmacokinetics/Toxixodynamic and Cystic Fibrosis mutational status

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

  4. Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

    Area Under the Effect Time curve (AUEC) of Lung Clearance Index 2.5

  5. Area Under the Effect Time curve (AUEC) of Sweat Chloride

    Time frame: 5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing

Study contacts

Contact information is provided by the study sponsor or research team.

Philippe REIX, M.D., Ph.D

CONTACT

[email protected]

+33 4 27 85 54 70

Romain GARREAU, PharmD.

CONTACT

[email protected]

+33 4 72 07 19 28

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: IMPROVED

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Dec 26, 2025
Registry last updated
Feb 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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