The clinical efficacy of CFTR modulating drugs is limited, some patients respond, while others do not or have side effects. The inter-individual variability (IIV) in the PK seems large, and therefore we hypothesize that we might be over- or…
ID
Bron
Verkorte titel
Aandoening
Cystic Fibrosis
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
To assess the exposure (AUC, Cmax) of tezacaftor-ivacaftor in a real life clinical setting in paediatric CF patients
Achtergrond van het onderzoek
There are novel medicines in CF that target the CF transmembrane conductance regulator (CFTR) and increase its activity. Thesedrugs improve the lung function, quality of life and body mass index in patients with specific mutations and might decreasepulmonary exacerbations. The combination of tezacaftor-ivacaftor (Symkevi®) is registered for patients ≥ 12 years old and theexpectation is that at the end of 2020 it will also be registered for children from the age of 6 years. The clinical efficacy of thesedrugs is limited, some patients respond, while others do not or have side effects. The inter-individual variability (IIV) seems largeand therefore this study hypothesizes that we might be over- or undertreating specific groups of patients, which can affect efficacy,side effects and costs of these expensive drugs. Very little is known about the pharmacokinetics (PK) of tezacaftor-ivacaftor,especially in the paediatric population. Better knowledge of the PK may provide more insight into the exposure-responserelationships and IIV.
Doel van het onderzoek
The clinical efficacy of CFTR modulating drugs is limited, some patients respond, while others do not or have side effects. The inter-individual variability (IIV) in the PK seems large, and therefore we hypothesize that we might be over- or undertreating specific groups of patients, which can affect efficacy and side effects these drugs. There
Onderzoeksopzet
0, 3, 6, 9, 12 months
Onderzoeksproduct en/of interventie
The intervention consists of additional DBS blood sampling for PK analysis.
Algemeen / deelnemers
Wetenschappers
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Use a combination therapy of tezacaftor-ivacaftor for a minimum period of 8 days in regular care or compassionate use
- CF patients aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G,
- 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.
- Signed informed consent from the patient when ≥16 years, from the patient and both parents for patients aged 12-15 years, from both parents aged 6-11 years.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- History of poor compliance deemed by the physician
- Concomitant use of drugs that have an inhibitory or inducing effect on the CYP3A4 enzyme metabolism 14 days before the blood collection, if the patient uses one or more of these medicines the blood collection of the upcoming visit will be skipped:
o Inducers of CYP3A: rifampicin, rifabutin, phenobarbital, carbamazepine, phenytoin and St. John’s wort
o Inhibitors of CYP3A: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin, fluconazole, erythromycin and grapefruit juice
- Patient or parent refusal
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL9426 |
| Ander register | METC AMC : METC 2021_021 |