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

NCT01258504 | Completed Results

• 2 other identifiers: K3302010-022328-64
• Study Type: observational
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Interactions

Keywords

Steady-state; Bosentan; St. Johns Wort

Outcome Measures

Primary Outcomes (2)

• AUC of Bosentan

  0-infinity; during dosing interval

• Cmax of Bosentan

  after first dose, at steady-state and during SJW

Study Arms (2)

CYP2C9 wild type

CYP2C9 wild type ="extensive metaboliser" * 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 St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20

Drug: St. Johns Wort

CYP2C9 mutant

CYP2C9 \*2/\*2 or 2\*/\*3 or \*3/\*3 = "poor metaboliser" * 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 St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20

Drug: St. Johns Wort

Interventions

St. Johns Wort DRUG

* 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

Also known as: Jarsin

CYP2C9 mutant; CYP2C9 wild type

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

healthy subjects

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Gerd Mikus: lead

Study Sites (1)

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

Related Publications (1)

• Dingemanse J, van Giersbergen PL. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089-115. doi: 10.2165/00003088-200443150-00003.

  PMID: 15568889 BACKGROUND

MeSH Terms

Interventions

Hypericum extract LI 160

Limitations and Caveats

Interindividual changes of the interaction were large suggesting that close monitoring of bosentan effects is advisable because in a sizeable fraction of volunteers the exposure to bosentan was reduced.

Results Point of Contact

• Title: Prof. Dr. med. Gerd Mikus
• Organization: University of Heidelberg

gerd.mikus@med.uni-heidelberg.de

4962215639197

Study Officials

• Gerd Mikus, Prof. Dr.

  deputy head of department

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Clinical Research Unit

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: January 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2012
• Last Updated: May 31, 2017
• Results First Posted: June 2, 2015

Record last verified: 2017-05

Locations

DE (1)