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ID
Source
Brief title
Health condition
Cystic Fibrosis
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the exposure (AUC, Cmax) of tezacaftor-ivacaftor in a real life clinical setting in paediatric CF patients
Secondary outcome
1) To evaluate the relationship between covariates and PK parameters in order to explain inter-patient variability
2) To evaluate the relationship between AUC and through levels
3) To compare drug exposure in children of different age groups and compare with that in adults
4) To explore if there is a correlation between drug concentrations and clinical outcome measures (efficacy like exacerbation frequency, increase in weight, lung
Background summary
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.
Study objective
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
Study design
0, 3, 6, 9, 12 months
Intervention
The intervention consists of additional DBS blood sampling for PK analysis.
Inclusion criteria
- 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.
Exclusion criteria
- 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
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL9426 |
| Other | METC AMC : METC 2021_021 |