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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gerd Mikus, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01258504
First received: December 10, 2010
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

The aim of the present study is to assess the impact of the cytochrome P450 2C9 (CYP2C9) genotype (*2 and *3 allele versus wild type; ~3-5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-induction by St. John's wort (SJW) on steady state bosentan which is a CYP3A4 inducer itself.


Condition Intervention
Drug Interaction
Drug: St. John's wort (SJW)

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Bosentan

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Effect of St. John's wort on bosentan pharmacokinetics at steady-state depending on CYP2C9 genotypes [ Time Frame: 20 days ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: January 2011
Study Completion Date: June 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
CYP2C9 wild type
CYP2C9 wild type ="extensive metaboliser"
Drug: St. John's wort (SJW)
  • Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19.
  • Administration of SJW: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20
CYP2C9 mutant
CYP2C9 *2/*2 or 2*/*3 or *3/*3 = "poor metaboliser"
Drug: St. John's wort (SJW)
  • Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19.
  • Administration of SJW: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20

  Eligibility

Ages Eligible for Study:   18 Years to 65 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 CYP2C9 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
  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: NCT01258504

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: NCT01258504     History of Changes
Other Study ID Numbers: K330, 2010-022328-64
Study First Received: December 10, 2010
Last Updated: January 28, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

Additional relevant MeSH terms:
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014