Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Steady State Bosentan Before and During CYP3A4-inhibition by Clarithromycin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gerd Mikus, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01425229
First received: August 26, 2011
Last updated: January 21, 2013
Last verified: January 2013
  Purpose

The aim of the present study is to assess the impact of the OATP1B1 genotype (SLCO1B1*15 vs. wild type; ~2% SLCO1B1*15 haplotypes in Caucasian population) and the CYP2C9 genotype (*2 and *3 allele vs. wild type; ~5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-inhibition by clarithromycin on steady state bosentan which is a CYP3A4 inducer itself.

This study will focus on differential effects of genotypes and co-medication on the pharmacokinetics of bosentan at the metabolic and transport level. Participants will be genotyped for CYP2C9 (inclusion criterion), OATP1B1 (inclusion criterion), and CYP3A5 (no inclusion criterion).


Condition
Drug Interaction
Steady-state
Bosentan

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective

Further study details as provided by Heidelberg University:

Estimated Enrollment: 24
Study Start Date: June 2011
Study Completion Date: December 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
  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 × 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 and OATP1B1 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01425229

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

No publications provided

Responsible Party: Gerd Mikus, Prof. Dr. med. Gerd Mikus, University of Heidelberg
ClinicalTrials.gov Identifier: NCT01425229     History of Changes
Other Study ID Numbers: K318, 2010-021392-93
Study First Received: August 26, 2011
Last Updated: January 21, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

ClinicalTrials.gov processed this record on October 01, 2014