Drug-drug interaction between ciclosporin, fluconazole, and rivaroxaban. Healthy volunteers.
Conditions
Interventions
Group 1: Rivaroxaban, 20 mg p.o., single dose (three times during the study).
Ciclosporin p.o., for 16-24 days (individually adjusted dose).
Fluconazole 400 mg p.o., for 10-14 days.
Sponsors
Universität Heidelberg, Medizinische Fakultät
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Age 18 – 64 y BMI 18 to 30 kg/m2 and body weight of >=50 kg. Good state of health (physically and mentally). No clinically relevant findings in any of the investigations of the pre-trial examination. Willingness to follow specified dietary restrictions. Willingness to abstain from blood donation during and two month after the trial. Males and females of child-bearing potential are only included if they use reliable contraception with a Pearl Index <1 % (i.e. two independent effective contraceptive methods) during the trial and for two weeks after the last administration of trial medication. 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 metabolising enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or two weeks, whatever is longer. Regular drug intake. Exceptions are: contraceptive drugs, iodine, thyroid hormones (which will be documented and whose doses must be unchanged throughout the trial). Other exceptions may be made after careful consideration of potential effects of the drug under consideration on metabolic enzymes and drug transporters and of potential risks due to effects of the trial drugs on the drug under investigation. 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 findings in the pre-trial examination, especially any condition known or expected to modify absorption, distribution, metabolism, or excretion of the drug under investigation. Any sign or symptom indicating an undue risk (in the opinion of the investigator). Known or suspected inability to provide complete urine collections. Any factor presumably interfering with the trial aims (in the opinion of the investigator). Haemoglobin 440 ms (males) or >460 ms (females). History of ventricular arrhythmia (including torsades de pointes; isolated ventricular extrasystoles are not an exclusion criterion). History of hypersensitivity to fluconazole or further ingredients of the drug formulation. History of hypersensitivity to itraconazole, ketoconazole, voriconazole, or related drugs. History of hypersensitivity to midazolam or further ingredients of the drug formulation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Increase in rivaroxaban exposure (AUC) during cotreatment with ciclosporin. Increase in rivaroxaban exposure (AUC) during cotreatment with ciclosporin and fluconazole. | — |
Secondary
| Measure | Time frame |
|---|---|
| Determinants of the individual extent of the drug-drug interaction, such as CYP3A phenotype. Effects of 400 mg fluconazole daily on ciclosporin PK. Relationship between ciclosporin concentrations and PD markers of ciclosporin effects, | — |
Countries
Germany
Contacts
Public ContactDavid Czock
Universitätsklinikum Heidelberg, Abteilung Klinische Pharmakologie und Pharmakoepidemiologie
Outcome results
None listed