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

NCT07303621 | Recruiting

• 2 other identifiers: 69HCL25_07082025-A01805-44
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cystic Fibrosis (CF)

Keywords

Trikafta; Elexacaftor; Ivacaftor; Cystic Fibrosis; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor

  Measure residual concentration of Elexacaftor, Ivacaftor and Tezacaftor

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

• Maximum Plasma Concentration [Cmax]

  Measured Cmax 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 Elexacaftor, Ivacaftor and Tezacaftor

  Area under the concentration time curve between two administrations of (AUC0-tz) of Elexacaftor, Ivacaftor and Tezacaftor

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

Secondary Outcomes (5)

• 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 and Cystic Fibrosis mutational status and Adverse Event

  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

• 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

• 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

Study Arms (1)

Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics

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

Interventions

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

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

Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Study population is from a tertiary care hospital. Children enrolled in the study are followed in the referral center for pediatric cystic fibrosis.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Femme Mère Enfant (HFME)

Bron, 69029, France

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Central Study Contacts

Romain GARREAU, PharmD.

CONTACT

+33 4 72 07 19 28; romain.garreau@chu-lyon.fr

Philippe REIX, M.D., Ph.D

CONTACT

+33 4 27 85 54 70; philippe.reix@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 26, 2025
• Study Start: February 9, 2026
• Primary Completion (Estimated): August 9, 2027
• Study Completion (Estimated): August 9, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

FR (1)