Pharmacokinetic and Pharmacodynamic Interactions Between the Cholesterol-Lowering Ezetimibe and the Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz During Chronic Treatment in Healthy Volunteers With Reference to Intestinal Expression of CYP3A4, UGT1A1, ABCB1 and ABCC2
Information source: Ernst Moritz Arndt University of Greifswald
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pharmacokinetics; Drug Interactions; Pharmacodynamics; Intestinal Transporter Expression
Intervention: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany (Drug); 1 tablet Ezetrol(R) + 2 capsules Sustiva(R) (efavirenz) single dose, DuPont Pharma (Drug); tablet Ezetrol(R) and 2 capsules Sustiva(R) steady state (Drug)
Phase: Phase 1
Status: Not yet recruiting
Sponsored by: Ernst Moritz Arndt University of Greifswald Official(s) and/or principal investigator(s):
Werner Siegmund, Prof, Principal Investigator, Affiliation: Department of Clinical Pharmacology
Overall contact:
Christiane Modeß, Dr, Phone: +49 (0)3834 865659, Email: chrimo@uni-greifswald.de
Summary
The purpose of this study is to evaluate the effects of a chronic co-medication of efavirenz
on pharmacokinetics and sterol-lowering effects of ezetimibe at steady-state in healthy
subjects genotyped for ABCB1, ABCC2, CYP2B6 and UGT1A1.
Clinical Details
Study design: Basic Science, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Primary outcome: Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for efavirenz: AUC0-∞, Cmax
Secondary outcome: Second. characteristics: for ezetimibe and efavirenz: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and efavirenz: AUC0-t, t½, tmax
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- age: 18 - 45 years
- sex: male and female
- ethnic origin: Caucasian
- body weight: 19 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:
- existing cardiac or haematological diseases and/or pathological findings, which might
interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
- existing hepatic and renal diseases and/or pathological findings, which might
interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
- existing gastrointestinal diseases and/or pathological findings, which might interfere
with the drug's safety, tolerability, absorption and/or pharmacokinetics
- 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 anti-HIV-test, HBs-Ag-test or anti-HCV-test
- 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
Locations and Contacts
Christiane Modeß, Dr, Phone: +49 (0)3834 865659, Email: chrimo@uni-greifswald.de
Department of Clinical Pharmacology, Greifswald 17489, Germany
Additional Information
Starting date: March 2009
Ending date: March 2010
Last updated: December 17, 2008
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