Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects - Full Text View

Sponsor:	Ernst Moritz Arndt University of Greifswald
Information provided by:	Ernst Moritz Arndt University of Greifswald
ClinicalTrials.gov Identifier:	NCT00621699

Purpose

The purpose of this study is to confirm a significant influence of ezetimibe and tacrolimus on each others pharmacokinetics

Condition	Intervention	Phase
Pharmacokinetics Drug Interactions Hypercholesterolemia Immunosuppression	Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany Drug: 1 capsule Prograf(R) (tacrolimus), Astellas Pharma GmbH, Germany Drug: 1 tablet Ezetrol(R) + 1 capsules Prograf(R)	Phase I

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: hypercholesterolemia

MedlinePlus related topics: Bowel Movement Cholesterol Urine and Urination

Drug Information available for: Tacrolimus anhydrous Tacrolimus Ezetimibe

U.S. FDA Resources

Further study details as provided by Ernst Moritz Arndt University of Greifswald:

Primary Outcome Measures:

Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for tacrolimus: AUC0-∞, Cmax [ Time Frame: September 2007 to November 2007 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and tacrolimus: AUC0-t, t½, tmax [ Time Frame: September 2007 to November 2007 ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	September 2007
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
C: Experimental administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 1 capsule Prograf(R) (5 mg tacrolimus)	Drug: 1 tablet Ezetrol(R) + 1 capsules Prograf(R) administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 1 capsule Prograf(R) (5 mg Tacrolimus), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
A: Active Comparator administration of 1 tablet Ezetrol(R) (10 mg ezetimibe)	Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany administration of 1 tablet Ezetrol(R) (10 mg ezetimibe), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
B: Active Comparator administration of 1 capsule Prograf(R) (5 mg tacrolimus)	Drug: 1 capsule Prograf(R) (tacrolimus), Astellas Pharma GmbH, Germany administration of 1 capsule Prograf(R) (5 mg tacrolimus), 0-144 h blood sampling

Detailed Description:

Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as tacrolimus. To prevent increased cardiovascular morbidity and mortality in these patients, co-medication with lipid-lowering statins is recommended. However, treatment with statins is limited in many patients by insufficient cholesterol-lowering efficacy, drug interactions and serious adverse drug reactions (e.g. rhabdomyolysis). These patients may benefit from comedication with the cholesterol absorption inhibitor ezetimibe. Since tacrolimus and ezetimibe were shown to be substrates of the efflux transporter ABCB1 (P-glycoprotein), drug interactions between both compounds may occur. Therefore, this clinical study in healthy subjects was initiated to evaluate the clinical relevance of drug/drug interactions between tacrolimus and ezetimibe according to the accepted bioequivalence approach.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

age: 18 - 45 years
sex: male and female
ethnic origin: Caucasian
body weight: 19 kg/m² to 27 kg/m²
good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
written informed consent

Exclusion Criteria:

known allergy to macrolide antibiotics
existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
acute or chronic diseases which could affect drug absorption or metabolism
history of any serious psychological disorder
drug or alcohol dependence
positive drug or alcohol screening
smokers of 10 or more cigarettes per day
positive screening results for HIV, HBV and HCV
volunteers who are on a diet which could affect the pharmacokinetics of the drug
heavy tea or coffee drinkers (more than 1L per day)
lactation and pregnancy test positive or not performed
volunteers suspected or known not to follow instructions
volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
volunteers liable to orthostatic dysregulation, fainting, or blackouts
blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study
participation in a clinical trial during the last 3 months prior to the start of the study
less than 14 days after last acute disease
any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists)
intake of grapefruit containing food or beverages within 7 days prior to administration
known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
subjects with severe allergies or multiple drug allergies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621699

Locations

Germany
Department of Clinical Pharmacology
Greifswald, Germany, 17487

Sponsors and Collaborators

Ernst Moritz Arndt University of Greifswald

Investigators

Principal Investigator:

Werner Siegmund, Prof

Department of Clinical Pharmacology

More Information

No publications provided

Responsible Party:	Department of Clinical Pharmacology ( Prof. Dr. W. Siegmund, MD )
Study ID Numbers:	Eze-Tacro, 2006-006549-14
Study First Received:	February 12, 2008
Last Updated:	February 12, 2008
ClinicalTrials.gov Identifier:	NCT00621699 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ernst Moritz Arndt University of Greifswald:

pharmacokinetics
drug interactions
ezetimibe
tacrolimus
human experimentation

Additional relevant MeSH terms:

Antimetabolites
Hyperlipidemias
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antilipemic Agents
Physiological Effects of Drugs
Ezetimibe

Tacrolimus
Anticholesteremic Agents
Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on November 25, 2009