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: University Medicine Greifswald
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pharmacokinetics; Drug Interactions; Pharmacodynamics; Intestinal Transporter Expression
Intervention: Ezetrol (ezetimibe) multiple dose (Drug); Ezetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose (Drug); Ezetrol (ezetimibe) and Sustiva (efavirenz) multiple dose (Drug); Sustiva (efavirenz) single dose (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: University Medicine Greifswald Official(s) and/or principal investigator(s): Werner Siegmund, Prof, Principal Investigator, Affiliation: Department of Clinical Pharmacology
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: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30
Secondary outcome: AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
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
Department of Clinical Pharmacology, Greifswald 17489, Germany
Additional Information
Starting date: March 2009
Last updated: September 23, 2010
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