E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
patients with cystic fibrosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the pharmacokinetic interaction of elexacaftor/tezacaftor/ivacaftor and tacrolimus in adult CF patients using tacrolimus after renal or liver transplantation by: - quantitating the effect of elexacaftor/tezacaftor/ivacaftor on the bioavailability of tacrolimus in CF patients with a history of liver or kidney transplantation and current on tacrolimus treatment. - quantitating the dose adjustment of tacrolimus during co-administration of elexacaftor/tezacaftor/ivacaftor.
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E.2.2 | Secondary objectives of the trial |
- To investigate the clinical effect of elexacaftor/tezacaftor/ivacaftor in CF patients using tacrolimus after renal or liver transplantation. - To quantitate the exposure to elexacaftor/tezacafor/ivacaftor in week 1, 2, 3 and 4 after starting elexacaftor/tezacaftor/ivacaftor. - To quantitate the number of side effects (adverse events and serious adverse events) when when co-administrating the elexacftor/tezacaftor/ivacaftor with tacrolimus.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Males and females aged 18 years or older on the date of informed consent -Diagnosis of cystic fibrosis with a genotype registered for the use of elexacaftor/tezacaftor/ivacaftor confirmed by genotype analysis. -Kidney or liver transplantation > 1 year ago -Current use of tacrolimus -Signed informed consent form (ICF)
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E.4 | Principal exclusion criteria |
-Use of drugs that are metabolized by the CYP3A enzyme or have a known influence on the CYP3A enzyme (inducers or inhibitors) -Having a contra indication for the use of elexacaftor/tezacaftor/ivacaftor -Organ rejection within the last 3 months -Pulmonary exacerbation within one month before the study period (defined as need for intravenous antibiotics) -Pregnancy or lactation -Pregnancy wish
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E.5 End points |
E.5.1 | Primary end point(s) |
- Pharmacokinetic parameters: T1/2, Tmax, Cmax, Cmin, AUC all measured without and with co administration of elexacaftor/tezacaftor/ivacaftor in order to measure RAUC of tacrolimus (RAUC=AUCtacro with elexacaftor/tezacaftor/ivacaftor/AUCtacro) in week 1, 2, 3 and 4 after starting elexacaftor/tezacaftor/ivacaftor. Change in T1/2, Tmax, Cmax, Cmin after co-administration with elexacaftor/tezacaftor/ivacaftor measured in week 1, 2, 3 and 4 after starting elexacaftor/tezacaftor/ivacaftor. - Number and level of dose adjustments made in order to stay within target tacrolimus values.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at the end of the study period |
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E.5.2 | Secondary end point(s) |
- Absolute change in lung function (FVC and FEV1), absolute change in quality of life (CFQ), , absolute change in nutritional status (weight, BMI) in week 1, 2, 3 and 4 after starting elexacaftor/tezacaftor/ivacaftor. Absolute change in sweatchloride from baseline through end of the study. - Through concentrations of elexacaftor, tezacaftor and ivacaftor measured in week 1, 2, 3 and 4 after starting elexacaftor/tezacaftor/ivacaftor. - Safety and tolerability based on the number and type of (S)AEs, laboratory values and vital signs.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at the end of the study period |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
a single centre open label controlled clinical drug-drug interaction trial |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |