Interaction between food and tacrolimus. Healthy volunteers
Conditions
Interventions
Group 1: In this pharmacokinetic interaction study, four single doses of tacrolimus 5 mg are administered orally.
Arm 1: Sequence: Prograf, Envarsus, Prograf + breakfast, Envarsus + breakfast.
Group 2
Sponsors
Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Male or female Caucasian. • Age 18 to = 40 kg. • Good state of health (physically and mentally) as determined by medical assessment consisting of a medical history, physical examination, an ECG, and a laboratory evaluation that all show no clinically relevant abnormalities. • Known CYP3A5 genotype or participation in genotyping study. • No clinically relevant findings in any of the investigations of the SCR visit. • Agreement to abstain from St. John’s wort (Hypericum perforatum L.) during the time of the trial. • Agreement to follow specified dietary requirements (e.g. some citrus products, especially grapefruit, are not allowed). •Agreement to follow specified, highly effective contraceptive measures. • Able to communicate well with the investigator, to understand and comply with the requirements of the trial. • Voluntarily signed informed consent after full explanation of the trial to the participant.
Exclusion criteria
Exclusion criteria: • Intake of a substance known to induce or inhibit drug metabolizing enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or two weeks, whatever is longer (except oral contraceptives or levothyroxine). • Any physical disorder that could interfere with the participant’s safety during the clinical trial or with the trial objectives. • Any acute or chronic illness or clinically relevant finding in the pre-trial examination known or expected to modify absorption, distribution, metabolism, or excretion of the drug under investigation. • QTcF > 440 ms (males) or > 460 ms (females). • Regular smoking. • Excessive alcohol drinking (more than approximately 20 g/d alcohol). • Any participation in an interventional clinical trial within the last 4 weeks before inclusion. • Blood donation within 4 weeks (males) or 8 weeks (females) before the first trial day (refers to whole blood or red blood cell donation; plasma and/or platelet donation are considered acceptable). • Pregnancy or lactation. • Known intolerance to tacrolimus, midazolam, or further ingredients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in tacrolimus exposition (AUC0-inf) due to food. Comparison after administration of two different tacrolimus preparations (Envarsus® and Prograf®). (AUC0-inf = area under the curve, extrapolated to infinity). | — |
Secondary
| Measure | Time frame |
|---|---|
| Factors that may be associated with the individual degree of the drug-drug interaction (e.g. CYP3A phenotype, rs776746 polymorphism). | — |
Countries
Germany
Contacts
Public ContactDavid Czock
Universitätsklinikum Heidelberg, Abteilung Klinische Pharmakologie und Pharmakoepidemiologie
Outcome results
None listed