Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin (IMAGINE)

This study has been completed.
Sponsor:
Collaborator:
Groupe de Recherche sur la Thrombose
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:
NCT01385683
First received: June 27, 2011
Last updated: March 21, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Dabigatran then dabigatran and clarithromycin
Drug: Clarithromycin and dabigatran then dabigatran
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Official Title: Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome Measures:
  • Determination of dabigatran and its metabolites in plasma by LC/MS-MS method [ Time Frame: At Day 4 and Day 11 ] [ Designated as safety issue: No ]
    Calculating the area under the curve (AUC) from plasma concentrations of dabigatran versus time by the trapezoidal method. Determination of maximum concentration (Cmax)


Secondary Outcome Measures:
  • Pharmacodynamic parameters [ Time Frame: At Day 4 and Day 11 ] [ Designated as safety issue: No ]
    Measures activated Partial Thromboplastin Time (aPTT)and measures ECarin Time (ECT),

  • Genotyping [ Time Frame: At Day 1 ] [ Designated as safety issue: No ]
    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


Enrollment: 10
Study Start Date: June 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Dabigatran then dabigatran and clarithromycin
Drug: Dabigatran then dabigatran and clarithromycin
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)
Other Names:
  • Dabigatran (Pradaxa)75 mg
  • Clarithromycin (Zeclar) 500 mg
Active Comparator: Arm B
Clarithromycin and dabigatran and dabigatran
Drug: Clarithromycin and dabigatran then dabigatran
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.
Other Names:
  • Dabigatran (Pradaxa) 75 mg
  • Clarithromycin (Zeclar) 500 mg

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385683

Locations
France
Service de Medecine et Therapeutique
Saint-Etienne, France, 42055
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Groupe de Recherche sur la Thrombose
Investigators
Principal Investigator: Patrick MISMETTI, MD PhD CHU de Saint-Etienne
Study Chair: Xavier DELAVENNE, Pharmacist CHU de Saint-Etienne
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT01385683     History of Changes
Other Study ID Numbers: 1008073, 2010-024047-33
Study First Received: June 27, 2011
Last Updated: March 21, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Healthy volunteer
Pharmacokinetic
pharmacodynamic
Polymorphism, Genetic

Additional relevant MeSH terms:
Clarithromycin
Dabigatran
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants
Hematologic Agents

ClinicalTrials.gov processed this record on September 16, 2014