Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: 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

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.


Eligibility: 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

Relevance to patient case: not relevant