Overview
Influence of Cytochrome CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Ambrisentan
Status:
Completed
Completed
Trial end date:
2012-12-01
2012-12-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
The aim of the present study is to assess the impact of CYP3A4-induction by SJW on steady state ambrisentan and the impact of the cytochrome P450 2C19 (CYP2C19) genotype (*2 and *3 allele vs. wild type; ~2-5% poor metabolisers in Caucasian population) on the pharmacokinetics of ambrisentan in healthy volunteers.Accepts Healthy Volunteers?
Accepts Healthy VolunteersDetails
Lead Sponsor:
Gerd Mikus
Criteria
Inclusion Criteria:- Good state of health (physically and mentally)
- Able to communicate well with the investigator, to understand and comply with the
requirements of the study
- Voluntarily signed informed consent after full explanation of the study to the
participant.
- No clinically relevant findings in any of the investigations of the pre-study
examination, especially aminotransferase elevations ≥ 3 × upper limit of normal (ULN).
Minor deviations of other laboratory values from normal range may be acceptable, if
judged by the investigator to be of no clinical relevance.
- Known genotype for CYP2C19 polymorphism.
- Agreement to abstain from alcoholic beverages during the time of the study.
- Females must agree to use a reliable contraception (Pearl Index <1%), e.g. double
barrier method.
Exclusion Criteria:
- Any regular drug treatment within the last two months, except for oral contraceptives
in female volunteers and L-thyroxine.
- Any intake of a substance known to induce or inhibit drug metabolising enzymes or drug
transporters within a period of less than 10 times the respective elimination
half-life or 2 weeks, whatever is longer
- Any participation in a clinical trial within the last month before inclusion
- Any physical disorder which could interfere with the participant's safety during the
clinical trial or with the study objectives
- Any acute or chronic illness, or clinically relevant findings in the pre-study
examination, especially: a) any condition, which could modify absorption,
distribution, metabolism, or excretion of the drug regimen under investigation b)
Allergies (except for mild forms of hay fever) or history of hypersensitivity
reactions
- Regular smoking
- Blood donation within 6 weeks before first study day
- Excessive alcohol drinking (more than approximately 20 g alcohol per day)
- Inability to communicate well with the investigator due to language problems or poor
mental development
- Inability or unwillingness to give written informed consent
- Known or planned pregnancy or breast feeding
- Pre-existing moderate or severe liver impairment
- Contraindication against midazolam, ambrisentan, or SJW or any known intolerance to
any of these substances or their additives