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).