Population Pharmacokinetics of Elexacaftor-tezacaftor-ivacaftor in a Paediatric Population
ConditionCystic Fibrosis (CF)
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2-17
SponsorHospices Civils de Lyon
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Children aged 2 to 17 years old
Having Cystic Fibrosis
Treated by Elexacaftor/Tezacaftor and Ivacaftor (Trikafta® or Kaftrio®)
Disqualifiers
Allergy to previous CFTR modulator association (Ivacaftor, lumacaftor)
Pregnant women
Patient already enrolled in another study with CYP3A4 inhibitor
Pulmonary transplant recipient
Trial population
Study population is from a tertiary care hospital. Children enrolled in the study are followed in the referral center for pediatric cystic fibrosis.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
There is no intervention as this is a prospective pharmacokinetics study.
Other interventionThere is no intervention as this is a prospective pharmacokinetics study.
Treatment groups
150 Participants
are divided into 1 treatment groupGroup A: Trikafta, Elexacaftor, Ivacaftor, Tezacaftor, Cystic Fibrosis, Population pharmacokinetics1 intervention
Trial outcomes
Primary outcomes
1
Trough Concentration [Cmin] of Elexacaftor, Ivacaftor and Tezacaftor
Measure residual concentration of Elexacaftor, Ivacaftor and Tezacaftor
Time frame
5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing2
Maximum Plasma Concentration [Cmax]
Measured Cmax of Elexacaftor, Ivacaftor and Tezacaftor
Time frame
5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing3
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
Time frame
5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosingSecondary outcomes
1
Number (Proportion) of Subjects with adverse events
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
Time frame
5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosing2
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-dosing3
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-dosing4
Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations
Area Under the Effect Time curve (AUEC) of Lung Clearance Index 2.5
Time frame
5 minutes pre-dosing 3 to 4 hours post-dosing 6 to 7 hours post-dosingSponsors and contacts
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Source ClinicalTrials.gov