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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 18, 2014