Cystic fibrosis mucoviscoidosis
Conditions
Interventions
In phase 2, all subjects will receive a single dose of oral ivacaftor. In phase
3, all subjects will receive 7 doses of oral ritonavir an 1 dose of oral
ivacaftor. In phase 4, all subjects will rece
cystic fibrosis
Cytochrome P450 3A4
ivacaftor
Sponsors
HagaZiekenhuis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria for Healthy controls -Males and females, aged 18 years or older on the date of informed consent -No medical history and no medication -Signed informed consent form (ICF) - Able to understand and comply with protocol requirements, restrictions, and instructions, and likely to complete the study as planned, as judged by the investigator.;Inclusion criteria for 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) - Able to understand and comply with protocol requirements, restrictions, and instructions, and likely to complete the study as planned, as judged by the investigator
Exclusion criteria
Exclusion criteria: For both healthy controls as CF-patients the following exclusion criteria apply: - Use of ivacaftor - History of clinically significant cirrhosis with or without portal hypertension. - 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) ;For the Healthy controls an extra Exclusion Criterium applies: - Blood relationship in the first or second degree with a CF-patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. Other study parameters * Age * Gender * Height * Weight * Pregnancy test (if applicable) | — |
Countries
The Netherlands
Outcome results
None listed