Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Ambrisentan

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gerd Mikus, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01311362
First received: March 8, 2011
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Drug Interaction
Drug: St. Johns wort
Phase 1

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Influence of CYP3A4-induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Ambrisentan

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Effect of induction by SJW on ambrisentan steady-state kinetics and its relationship to CYP2C19 genotype [ Time Frame: 20 days ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: March 2011
Study Completion Date: December 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
CYP2C19 wild type
CYP2C19 wild type ="extensive metaboliser"
Drug: St. Johns wort
  • Administration of ambrisentan: 5 mg p.o. q.d. on day 1 and days 3-20
  • Administration of SJW: 300 mg p.o. three times a day (t.i.d.) on days 11-20
CYP2C19 mutant
CYP2C19 *2/*2 or *2/*3 or *3/*3 = "poor metaboliser"
Drug: St. Johns wort
  • Administration of ambrisentan: 5 mg p.o. q.d. on day 1 and days 3-20
  • Administration of SJW: 300 mg p.o. three times a day (t.i.d.) on days 11-20

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

healthy subjects

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01311362

Locations
Germany
University Hospital Heidelberg
Heidelberg, Germany, 69120
Sponsors and Collaborators
Gerd Mikus
  More Information

Publications:
Responsible Party: Gerd Mikus, Head of Clinical Research Unit, University of Heidelberg
ClinicalTrials.gov Identifier: NCT01311362     History of Changes
Other Study ID Numbers: K331, 2010-022868-13
Study First Received: March 8, 2011
Last Updated: January 28, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heidelberg University:
Steady-state
Ambrisentan
St. Johns Wort

ClinicalTrials.gov processed this record on April 15, 2014