Drug InteractionsNCT01425229
Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Bosentan Before and During Clarithromycin
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 OATP1B1 genotype (SLCO1B1*15 vs. wild type; ~2% SLCO1B1*15 haplotypes in Caucasian population) and the CYP2C9 genotype (*2 and *3 allele vs. 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?
- Bosentan
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2011to Dec 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 × 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.
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 OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Steady State Bosentan Before and During CYP3A4-inhibition by Clarithromycin
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).
- Conditions
- Drug Interactions
- Being tested
- Bosentan
- Keywords
- steady state, bosentan, clarithromycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Tracleer
- Administration of bosentan: 1 x 125 mg p.o. on day 1, 2 x 125 mg p.o. on day 2-14
- Administration of clarithromycin: 2 x 500 mg p.o. on day 11-14
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Haplotypes of CYP2C9 and OATP1B1 characterisation of CYP2C9 (CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910)) and OATP1B1 (SLCO1B1*15 (rs2306283, rs4149056)) Receives: Drug: Bosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
AUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
Measured: 0-infinity; dosing interval
Cmax
Cmax after the first dose of bosentan, at steady-state, during clarithromycin
Measured: after first dose, at steady-state, during clarithromycin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startJun 2011
- Primary completionMay 2012
- Study completionDec 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 16 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
- NCT01425229
- Sponsor's protocol ID
- K318
- Other IDs
- 2010-021392-93
- Status last verified
- May 2017
- First submitted
- 26 Aug 2011
- 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 OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Steady State Bosentan Before and During CYP3A4-inhibition by Clarithromycin
- ClinicalTrials.gov ID
- NCT01425229
- Acronym / sponsor ID
- K318
- Conditions
- Drug Interactions
- Keywords
- steady state, bosentan, clarithromycin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Gerd MikusUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- May 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 29 Aug 2011 (estimated)
- Results
- Posted 4 Aug 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 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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bosentan | – | Drug: BosentanHaplotypes of CYP2C9 and OATP1B1 characterisation of CYP2C9 (CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910)) and OATP1B1 (SLCO1B1*15 (rs2306283, rs4149056)) |
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 × 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.
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 |
|---|---|---|
| BosentanAlso: Tracleer* Administration of bosentan: 1 x 125 mg p.o. on day 1, 2 x 125 mg p.o. on day 2-14 * Administration of clarithromycin: 2 x 500 mg p.o. on day 11-14 | Drug | Bosentan |
Primary outcome
AUC
Time frame: 0-infinity; dosing interval
AUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
Cmax
Time frame: after first dose, at steady-state, during clarithromycin
Cmax after the first dose of bosentan, at steady-state, during clarithromycin
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.
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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 4 Aug 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 (time frame: 0-infinity; 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 NCT01425229, 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.