Cystic Fibrosis (CF)
Conditions
Keywords
Trikafta, Elexacaftor, Ivacaftor, Cystic Fibrosis, pharmacokinetics
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.
Interventions
OTHERThere is no intervention as this is a prospective pharmacokinetics study.
There is no intervention as this is a prospective pharmacokinetics study.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number (Proportion) of Subjects with adverse events | 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 |
| 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 Lung Clearance Index 2.5 |
| 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 | — |
Countries
France
Contacts
CONTACTRomain GARREAU, PharmD.
CONTACTPhilippe REIX, M.D., Ph.D
Outcome results
None listed