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Influence of Cytochrome CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Ambrisentan

Information source: Heidelberg University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: VA Drug Interactions [VA Drug Interaction]

Intervention: St. Johns wort (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Gerd Mikus

Official(s) and/or principal investigator(s):
Gerd Mikus, Prof. Dr., Principal Investigator, Affiliation: deputy head of department

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.

Clinical Details

Official title: Influence of CYP3A4-induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Ambrisentan

Study design: Observational Model: Case Control, Time Perspective: Prospective

Primary outcome:

AUC of Ambrisentan

Cmax of Ambrisentan

Eligibility

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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

Locations and Contacts

University Hospital Heidelberg, Heidelberg 69120, Germany
Additional Information

Related publications:

Spence R, Mandagere A, Richards DB, Magee MH, Dufton C, Boinpally R. Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther. 2010 Oct;88(4):513-20. doi: 10.1038/clpt.2010.120. Epub 2010 Sep 1.

Harrison B, Magee MH, Mandagere A, Walker G, Dufton C, Henderson LS, Boinpally R. Effects of rifampicin (rifampin) on the pharmacokinetics and safety of ambrisentan in healthy subjects: a single-sequence, open-label study. Clin Drug Investig. 2010;30(12):875-85. doi: 10.2165/11539110-000000000-00000.

Starting date: March 2011
Last updated: May 29, 2015

Page last updated: August 23, 2015

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