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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00621699
Other study ID # Eze-Tacro
Secondary ID 2006-006549-14
Status Completed
Phase Phase 1
First received February 12, 2008
Last updated February 12, 2008
Start date September 2007
Est. completion date November 2007

Study information

Verified date February 2008
Source University Medicine Greifswald
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 24
Est. completion date November 2007
Est. primary completion date November 2007
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 45 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science


Intervention

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
1 capsule Prograf(R) (tacrolimus), Astellas Pharma GmbH, Germany
administration of 1 capsule Prograf(R) (5 mg tacrolimus), 0-144 h blood sampling
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

Locations

Country Name City State
Germany Department of Clinical Pharmacology Greifswald

Sponsors (1)

Lead Sponsor Collaborator
University Medicine Greifswald

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Primary characteristics: for ezetimibe: AUC0-8, Cmax; for tacrolimus: AUC0-8, Cmax September 2007 to November 2007 No
Secondary Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-8, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and tacrolimus: AUC0-t, t½, tmax September 2007 to November 2007 No
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