Study design
Real-word data were prospectively collected in a multi-center,
observational PK study in a cohort of 21 cwCF using tezacaftor-ivacaftor
as chronic CF treatment. Between May 2021 and August 2022 cwCF were
enrolled from three Dutch hospitals. Main inclusion criteria were
children aged 6-17 years with at least one F508del -mutation, and
the use of tezacaftor-ivacaftor according to regular care protocols:
with tezacaftor-ivacaftor dosages of 100-300mg daily in children of ≥12
years and ≥6 years weighing ≥30kg, and 50-150mg in 6-11 years weighing
deemed by the physician, and concomitant use of drugs with inhibitory or
inducing effect on the CYP3A4 enzyme metabolism during 14 days before
blood collection. The study was approved by the Institutional Review
Board (ABR NL75811.018.21). Informed consent was obtained from all
participants and their parents or legal guardians prior to any
study-related procedures. Patients were included after a minimum of two
weeks treatment with tezacaftor-ivacaftor, in order to reach
steady-state concentrations. Patients were followed until they switched
to elexacaftor-tezacaftor-ivacaftor. To facilitate PK sampling, patients
and their parents were trained to perform dried blood spot (DBS)
sampling. At one time point during the study, DBS samples were taken at
home at T=0, 4 and 8 hours after administration of tezacaftor-ivacaftor
by the participant/parent(s). During every regular visit at the
outpatient clinic (~every three months), a single sample
was taken by venous or DBS sampling at a random time point after
administration of tezacaftor-ivacaftor. No additional venipunctures were
performed for PK analysis. Tezacaftor-ivacaftor administration and
sampling times were recorded, as well as adherence (self-reported and
physicians assessment) and the (fat) food with which
tezacaftor-ivacaftor was taken. Clinical data as part of regular care
were collected including patient demographics, CF-related
co-morbidities, co-medication and liver function tests (ALAT, ASAT,
bilirubin).