Drug InteractionsNCT01258504
Influence of CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Bosentan
An observational study of Drug Interactions, run by Gerd Mikus at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interactions
- What is being tested?
- St. Johns Wort
- How many people
- 13 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2011to Jun 2012
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: healthy subjects
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Bosentan
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.
Read the detailed description
We evaluate the effect of SJW on bosentan pharmacokinetics and its relationship to polymorphisms in the CYP2C9 gene known to reduce CYP2C9 activity. This study will be conducted at bosentan steady-state because concentrations decrease in the first 10 days of treatment due to auto-induction of the metabolism.
- Conditions
- Drug Interactions
- Being tested
- St. Johns Wort
- Keywords
- Steady-state, Bosentan, St. Johns Wort
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
St. Johns WortDrug
Also called Jarsin
- 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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: St. Johns Wort |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC of Bosentan
Measured: 0-infinity; during dosing interval
Cmax of Bosentan
Measured: after first dose, at steady-state and during SJW
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2010 (estimated)
- Study startJan 2011
- Primary completionDec 2011
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug InteractionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gerd Mikus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gerd Mikus, Heidelberg University
- Investigators
- Gerd Mikus, Prof. Dr., Principal investigator, deputy head of department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01258504
- Sponsor's protocol ID
- K330
- Other IDs
- 2010-022328-64
- Status last verified
- May 2017
- First submitted
- 10 Dec 2010
- Last updated
- 31 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 15568889
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Bosentan
- ClinicalTrials.gov ID
- NCT01258504
- Acronym / sponsor ID
- K330
- Conditions
- Drug Interactions
- Keywords
- Steady-state, Bosentan, St. Johns Wort
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Gerd MikusUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 13 Dec 2010 (estimated)
- Results
- Posted 2 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
We evaluate the effect of SJW on bosentan pharmacokinetics and its relationship to polymorphisms in the CYP2C9 gene known to reduce CYP2C9 activity. This study will be conducted at bosentan steady-state because concentrations decrease in the first 10 days of treatment due to auto-induction of the metabolism.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYP2C9 wild type | – | Drug: St. Johns WortCYP2C9 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 |
| CYP2C9 mutant | – | Drug: St. Johns WortCYP2C9 *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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- healthy subjects
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| St. Johns WortAlso: Jarsin* 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 | Drug | CYP2C9 mutant, CYP2C9 wild type |
Primary outcome
AUC of Bosentan
Time frame: 0-infinity; during dosing interval
Cmax of Bosentan
Time frame: after first dose, at steady-state and during SJW
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15568889Dingemanse 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.
Related trials for Drug Interactions
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Modeling Host-Pathogen Interaction Using Lymphoid Organoids
Staphylococcal Infections
RecruitingObservational study
Molecular Basis of Human Phagocyte Interactions With Bacterial Pathogens
Host Defense Mechanisms
RecruitingPhase 1
Safety and PK of Ceftibuten-ledaborbactam Etzadroxil Fixed-dose Combination
Healthy Volunteer, Pharmacokinetics
RecruitingPhase 1
A Study to Assess the Effects of Probenecid on the Pharmacokinetics of Mirdametinib and Its Metabolites in Healthy Participants
Healthy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerd Mikus, Prof. Dr. principal investigator
deputy head of department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Interactions, run by Gerd Mikus at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC of Bosentan (time frame: 0-infinity; during dosing interval). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01258504, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2017.