HealthyPhase 1IMAGINENCT01385683
Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
A Phase 1 study testing Dabigatran then dabigatran and clarithromycin and Clarithromycin and dabigatran then dabigatran in people with Healthy, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
Trial summary
Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation and the treatment of venous thromboembolism. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dabigatran then dabigatran and clarithromycin and Clarithromycin and dabigatran then dabigatran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2011to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- affiliated or beneficiary of a social security category
- having signed the inform consent form
- having signed the genetic consent form
- weight between 60 and 85 kg
- normal clinical exam
- normal biological exam
Who cannot join
- contra-indication to dabigatran
- contra-indication to clarithromycin
- previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease
- smoker
- peptic ulcer
- severe liver disease
- severe kidney failure
- previous surgery within one month
Trial locations and contacts
1 site in 1 country.
About this study
Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation and the treatment of venous thromboembolism. It is administered with fixed dose and does not require laboratory monitoring because of the low inter and intra individual pharmacokinetic (PK) and pharmacodynamics (PD) of dabigatran. However, the bioavailability of dabigatran is very low (6.5%) and is controlled by an efflux protein, P-GP. This molecule has a genetic polymorphism. The inhibition of this protein can cause a significant increase in intestinal absorption of dabigatran and expose patients to a risk of bleeding by overdose. Two major drug interactions have been identified : quinidine (cons-indication) and amiodarone (precautions). It is likely that other interactions exist and can be clinically significant in patients not selected such as testing. The development of tools to study the influence of P-GP on the PK and PD of dabigatran is therefore interesting. As the P-GP has a genetic polymorphism, the study of the latter is an important element in the detection of drug interactions. In this sense, clarithromycin, a potent inhibitor of P-GP is a good model to evaluate the primary mechanism of drug interaction of dabigatran and optimize the experimental design of studies to be conducted.
- Conditions
- Healthy
- Being tested
- Dabigatran then dabigatran and clarithromycin, Clarithromycin and dabigatran then dabigatran
- Keywords
- Healthy volunteer, Pharmacokinetic, pharmacodynamic, Polymorphism, Genetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabigatran then dabigatran and clarithromycinDrug
Also called Dabigatran (Pradaxa)75 mg, Clarithromycin (Zeclar) 500 mg
D4 : dabigatran 300 mg (4 tablets) one time. D8 to D10 : Clarithromycin 500mg (1 tablet) twice daily. D11 : Clarithromycin 500mg (1 tablet) + 300mg dabigatran (4 tablets)
Clarithromycin and dabigatran then dabigatranDrug
Also called Dabigatran (Pradaxa) 75 mg, Clarithromycin (Zeclar) 500 mg
D1 to D3 : Clarithromycin 500mg (1 tablet) twice daily. D4 : Clarithromycin 500mg (1 tablet) + 300mg dabigatran (4 tablets). D11 : dabigatran 300 mg (4 tablets) one time.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Dabigatran then dabigatran and clarithromycin Receives: Drug: Dabigatran then dabigatran and clarithromycin |
| Arm B | Active comparator | Clarithromycin and dabigatran and dabigatran Receives: Drug: Clarithromycin and dabigatran then dabigatran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of dabigatran and its metabolites in plasma by LC/MS-MS method
Calculating the area under the curve (AUC) from plasma concentrations of dabigatran versus time by the trapezoidal method. Determination of maximum concentration (Cmax)
Measured: At Day 4 and Day 11
Secondary outcomes (2)
Pharmacodynamic parameters
Measures activated Partial Thromboplastin Time (aPTT)and measures ECarin Time (ECT),
Measured: At Day 4 and Day 11
Genotyping
Genotyping of MDR-1 (gene for P-GP): C3435T SNP of exon 26, SNP G2677T / A of exon 21 and C1236T SNP of exon 12
Measured: At Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Groupe de Recherche sur la Thrombose
- Responsible party
- Sponsor
- Investigators
- Patrick MISMETTI, MD PhD, Principal investigator, CHU de Saint-EtienneXavier DELAVENNE, Pharmacist, Study chair, CHU de Saint-Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385683
- Sponsor's protocol ID
- 1008073
- Other IDs
- 2010-024047-33
- Acronym
- IMAGINE
- Status last verified
- Mar 2012
- First submitted
- 27 Jun 2011
- Last updated
- 22 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
- ClinicalTrials.gov ID
- NCT01385683
- Acronym / sponsor ID
- IMAGINE / 1008073
- Conditions
- Healthy
- Keywords
- Healthy volunteer, Pharmacokinetic, pharmacodynamic, Polymorphism, Genetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Groupe de Recherche sur la Thrombose
- Study start
- Jun 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 30 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation and the treatment of venous thromboembolism. It is administered with fixed dose and does not require laboratory monitoring because of the low inter and intra individual pharmacokinetic (PK) and pharmacodynamics (PD) of dabigatran. However, the bioavailability of dabigatran is very low (6.5%) and is controlled by an efflux protein, P-GP. This molecule has a genetic polymorphism. The inhibition of this protein can cause a significant increase in intestinal absorption of dabigatran and expose patients to a risk of bleeding by overdose. Two major drug interactions have been identified : quinidine (cons-indication) and amiodarone (precautions). It is likely that other interactions exist and can be clinically significant in patients not selected such as testing. The development of tools to study the influence of P-GP on the PK and PD of dabigatran is therefore interesting. As the P-GP has a genetic polymorphism, the study of the latter is an important element in the detection of drug interactions. In this sense, clarithromycin, a potent inhibitor of P-GP is a good model to evaluate the primary mechanism of drug interaction of dabigatran and optimize the experimental design of studies to be conducted.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Dabigatran then dabigatran and clarithromycinDabigatran then dabigatran and clarithromycin |
| Arm B | Active comparator | Drug: Clarithromycin and dabigatran then dabigatranClarithromycin and dabigatran and dabigatran |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- affiliated or beneficiary of a social security category
- having signed the inform consent form
- having signed the genetic consent form
- weight between 60 and 85 kg
- normal clinical exam
Key exclusion criteria (8 listed)
- contra-indication to dabigatran
- contra-indication to clarithromycin
- previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease
- smoker
- peptic ulcer
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 |
|---|---|---|
| Dabigatran then dabigatran and clarithromycinAlso: Dabigatran (Pradaxa)75 mg, Clarithromycin (Zeclar) 500 mgD4 : dabigatran 300 mg (4 tablets) one time. D8 to D10 : Clarithromycin 500mg (1 tablet) twice daily. D11 : Clarithromycin 500mg (1 tablet) + 300mg dabigatran (4 tablets) | Drug | Arm A |
| Clarithromycin and dabigatran then dabigatranAlso: Dabigatran (Pradaxa) 75 mg, Clarithromycin (Zeclar) 500 mgD1 to D3 : Clarithromycin 500mg (1 tablet) twice daily. D4 : Clarithromycin 500mg (1 tablet) + 300mg dabigatran (4 tablets). D11 : dabigatran 300 mg (4 tablets) one time. | Drug | Arm B |
Primary outcome
Determination of dabigatran and its metabolites in plasma by LC/MS-MS method
Time frame: At Day 4 and Day 11
Calculating the area under the curve (AUC) from plasma concentrations of dabigatran versus time by the trapezoidal method. Determination of maximum concentration (Cmax)
2 secondary outcomes
Pharmacodynamic parameters
Time frame: At Day 4 and Day 11
Genotyping
Time frame: At Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2012.
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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.
Patrick MISMETTI, MD PhD principal investigator
CHU de Saint-Etienne
Xavier DELAVENNE, Pharmacist study chair
CHU de Saint-Etienne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dabigatran then dabigatran and clarithromycin and Clarithromycin and dabigatran then dabigatran in people with Healthy, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
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 6 inclusion and 8 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 22 Mar 2012. 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 France. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determination of dabigatran and its metabolites in plasma by LC/MS-MS method (time frame: At Day 4 and Day 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2012.