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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01311362
First Posted: March 9, 2011
Last Update Posted: May 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Gerd Mikus, Heidelberg University
  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
Drug Interactions Drug: St. Johns wort

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 Gerd Mikus, Heidelberg University:

Primary Outcome Measures:
  • AUC of Ambrisentan [ Time Frame: after first dose, at steady-state, during St John's wort ]
  • Cmax of Ambrisentan [ Time Frame: after first dose, at steady-state and during St John's wort ]

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"

  • Administration of ambrisentan: 5 mg p.o. q.d. on day 1 and days 3-20
  • Administration of St. Johns wort: 300 mg p.o. three times a day (t.i.d.) on days 11-20
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
Other Name: Jarsin
CYP2C19 mutant

CYP2C19 *2/*2 or *2/*3 or *3/*3 = "poor metaboliser"

  • Administration of ambrisentan: 5 mg p.o. q.d. on day 1 and days 3-20
  • Administration of St. Johns wort: 300 mg p.o. three times a day (t.i.d.) on days 11-20
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
Other Name: Jarsin

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01311362


Locations
Germany
University Hospital Heidelberg
Heidelberg, Germany, 69120
Sponsors and Collaborators
Gerd Mikus
Investigators
Principal Investigator: Gerd Mikus, Prof. Dr. deputy head of department
  More Information

Publications:
Responsible Party: Gerd Mikus, Head of Clinical Research Unit, Heidelberg University
ClinicalTrials.gov Identifier: NCT01311362     History of Changes
Other Study ID Numbers: K331
2010-022868-13 ( EudraCT Number )
First Submitted: March 8, 2011
First Posted: March 9, 2011
Results First Submitted: July 9, 2014
Results First Posted: June 2, 2015
Last Update Posted: May 31, 2017
Last Verified: May 2017

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


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