To assess whether IR-Tac and ER-Tac exhibit a different magnitude of drug-drug interaction after co-administration with voriconazole
ID
Source
Brief title
Condition
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess whether IR-Tac and ER-Tac exhibit a different magnitude of drug-drug
interaction after co-administration of voriconazole in lung, kidney, pancreas
or heart transplant recipients.
Secondary outcome
- To describe all relevant PK parameters for IR-Tac and ER-Tac, their
fold-change after azole initiation and the relevant azole PK parameters (which
are: Cmax, dose-adjusted Cmax, Cmin, dose-adjusted Cmin, Tmax, t1/2).
- To describe whether pharmacogenetic genotype and inflammatory markers have an
additional influence on tacrolimus and azole pharmacokinetics
- To investigate whether and with what extend the interaction diminishes over
time after discontinuation of the interacting drug, as measured with Cmin/dose
ratio
- To evaluate how tacrolimus dose should be adjusted at start and
discontinuation of the voriconazole, and how many dose adjustments are needed
for both formulations
Background summary
Tacrolimus treatment is delicate and increases risk of (invasive) fungal
infections, which need azole treatment. Tacrolimus and azoles exhibit drug-drug
interactions through CYP3A4/5 enzymes in gut and liver, increasing tacrolimus
exposure. The choice of tacrolimus formulation for immediate release tacrolimus
(IR-Tac) or extended release tacrolimus (ER-Tac) may influence the magnitude of
the interaction with voriconazole, as shown in healthy volunteers.
Study objective
To assess whether IR-Tac and ER-Tac exhibit a different magnitude of drug-drug
interaction after co-administration with voriconazole
Study design
Single center, observational open-label pharmacokinetic study with 4 parallel
arms.
Study burden and risks
The burden exists of extra time and extra blood sampling. There are no changes
in regular care. Because of the logistics, the start of the study may delay the
azole initiation with one day. This may not lead to addional risk of the
patient.
Benefits are increased therapeutic drug monitoring of the tacrolimus.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Lung, kidney, pancreas or heart transplant recipient
- Age >18 years
- Stable use of tacrolimus formulations Prograf/generic tacrolimus/Envarsus
- Indication for antifungal therapy with voriconazole
- Written informed consent
Exclusion criteria
- Administration of mTOR inhibitors, cyclosporine or quadruple immunosuppression
- Concomitant use of drugs that have a pharmacokinetic interaction with
tacrolimus
- Acute liver- or intestinal function impairment
- Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL75111.042.20 |
| Other | NTR: NL9080 |