The influence of cytochrome P450 3A4 inhibitors on serum levels of Ivacaftor in cystic fibrosis patients and healthy subjects.

Pharmacokinetic interactions between ivacaftor and cytochrome P450 3A4 inhibitors in cystic fibrosis patients and healthy controls - IACI

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-001440-18-NL

Enrollment

Registered

2018-01-16

Start date

2018-05-30

Completion date

Unknown

Last updated

2018-06-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

cystic fibrosis and healthy subjects

Interventions

Trade Name: Ivacaftor Pharmaceutical Form: Film-coated tablet Trade Name: claritromycin 500mg film coated tablets Product Name: Claritromycin Pharmaceutical Form: Film-coated tablet Trade Name: Azit

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Healthy controls -Males and females, aged 18 years or older on the date of informed consent -No medical history -Signed informed consent form (ICF) Cystic fibrosis patients -Males and females, aged 18 years or older on the date of informed consent -Cystic fibrosis (confirmed by genotype analysis, Class 1 and 2) -Exocrine pancreatic insufficiency -Signed informed consent form (ICF) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: -Use of ivacaftor -Hepatic impairment defined as (a history of) transaminase elevations -Severe renal impairment (creatinine clearance = 30 ml/min); -Use of drugs that are metabolized by the CYP3A enzyme or have a known influence on the CYP3A enzyme (inducers or inhibitors): see appendix. -Known allergy/intolerance to clarithromycin, ritonavir or azithromycin -Pregnancy or lactation -Pregnancy wish -Pulmonary exacerbation with hospital admission within one month before the study period (defined as need for intravenous antibiotics)

Design outcomes

Primary

Measure	Time frame
Main Objective: evaluate the effects of multiple doses of azithromycin, clarithromycin and nervier on the pharmacokinetics, safety and tolerability of a single oral dose of ivacaftor in healthy controls and in cystic fibrosis patients;Secondary Objective: -To calculate an optimal dosing scheme for ivacaftor therapy in cystic fibrosis patients when it is co-administered with a weak, strong and very strong CYP3A inhibitor. -To compare the results of healthy controls and cystic fibrosis patients. ;Primary end point(s): The principal outcome variable is the ratio (RAUC) of total area under the plasma concentration curve (AUC) for oral ivacaftor during co-administration of inhibitor (AUCI : ritonavir, clarithromycin and azithromycin) divided by the AUC in the control condition with no inhibitor (AUC0) : RAUC = (AUCI)/(AUC0) ;Timepoint(s) of evaluation of this end point: at the end of the study period.	—

Measure

Time frame

Main Objective: evaluate the effects of multiple doses of azithromycin, clarithromycin and nervier on the pharmacokinetics, safety and tolerability of a single oral dose of ivacaftor in healthy controls and in cystic fibrosis patients;Secondary Objective: -To calculate an optimal dosing scheme for ivacaftor therapy in cystic fibrosis patients when it is co-administered with a weak, strong and very strong CYP3A inhibitor. -To compare the results of healthy controls and cystic fibrosis patients. ;Primary end point(s): The principal outcome variable is the ratio (RAUC) of total area under the plasma concentration curve (AUC) for oral ivacaftor during co-administration of inhibitor (AUCI : ritonavir, clarithromycin and azithromycin) divided by the AUC in the control condition with no inhibitor (AUC0) : RAUC = (AUCI)/(AUC0) ;Timepoint(s) of evaluation of this end point: at the end of the study period.

—

Secondary

Measure	Time frame
Secondary end point(s): Number of adverse and serious adverse events The maximum observed plasma concentration (Cmax), the time to achieve Cmax (Tmax), the mean terminal half-life of ivacaftor. ;Timepoint(s) of evaluation of this end point: at the end of the study period.	—

Countries

Netherlands

Contacts

Public Contactdept of paediatric respir med

university medical center utrecht

k.vanderent@umcutrecht.nl

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026