Clinical trial NCT01385683: Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
Official title: Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteer
Pharmacokinetic
pharmacodynamic
Polymorphism, Genetic
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Groupe de Recherche sur la Thrombose
First posted: 2011-06-30
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief 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. 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.


Eligibility 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

Primary outcomes:
measure: Determination of dabigatran and its metabolites in plasma by LC/MS-MS method
timeFrame: At Day 4 and Day 11
Secondary outcomes:
measure: Pharmacodynamic parameters
timeFrame: At Day 4 and Day 11
measure: Genotyping
timeFrame: At Day 1
Other outcomes:
Locations:
city: Saint-Etienne
country: France
facility: Service de Medecine et Therapeutique
Study officials:
affiliation: CHU de Saint-Etienne
name: Patrick MISMETTI, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Saint-Etienne
name: Xavier DELAVENNE, Pharmacist
role: STUDY_CHAIR
References: