Effects of ciclosporin and its combination with fluconazole on the pharmacokinetics of rivaroxaban in healthy volunteers
- Conditions
- Drug-drug interaction between ciclosporin, fluconazole, and rivaroxaban.Healthy volunteers.
- Registration Number
- DRKS00011528
- Lead Sponsor
- niversität Heidelberg, Medizinische Fakultät
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 12
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.
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 <13 g/dl (males) or <12 g/dl (females).
Blood donation within 4 weeks (males) or within 8 weeks (females) before the first trial day.
Any participation in a clinical trial within the last month before inclusion.
Regular smoking and unwilling/unable to refrain from smoking during the duration of the trial.
Excessive alcohol drinking (more than approximately 20 g of alcohol per day).
Pregnancy or lactation.
Woman of childbearing potential unwilling/unable to use reliable methods of contraception.
Known intolerance to the trial drugs or further ingredients.
History of major bleeding, major trauma, or major surgical procedure of any type within the previous six months.
Clinically significant bleeding risk (e.g. signs and symptoms of gastric ulcer, tendency to nasal bleeding or menorrhagia).
Inherited or acquired bleeding disorder.
Uncontrolled, severe arterial hypertension.
Hereditary galactose intolerance, hereditary lactase deficiency, or hereditary glucose-galactose malabsorption.
History of hypersensitivity to rivaroxaban or further ingredients of the drug preparation.
Signs, symptoms, or laboratory values indicating acute or chronic infections.
Vaccination with live vaccines within the last 4 weeks.
Current of previous alcohol dependence.
History of hypersensitivity to ciclosporin or further ingredients of the drug preparation.
QTcF >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.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Increase in rivaroxaban exposure (AUC) during cotreatment with ciclosporin.<br>Increase in rivaroxaban exposure (AUC) during cotreatment with ciclosporin and fluconazole.
- Secondary Outcome Measures
Name Time Method Determinants of the individual extent of the drug-drug interaction, such as CYP3A phenotype.<br>Effects of 400 mg fluconazole daily on ciclosporin PK.<br>Relationship between ciclosporin concentrations and PD markers of ciclosporin effects,