Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Dabigatran then dabigatran and clarithromycin; Drug: Clarithromycin and dabigatran then dabigatran

• Registration Number: NCT01385683
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-06-27
• Study First Submitted QC: 2011-06-29
• Study First Posted: 2011-06-30
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-21
• Last Update Posted: 2012-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm A	Dabigatran then dabigatran and clarithromycin	Dabigatran then dabigatran and clarithromycin
Arm B	Clarithromycin and dabigatran then dabigatran	Clarithromycin and dabigatran and dabigatran

Primary Outcome Measures

Name	Time	Method
Determination of dabigatran and its metabolites in plasma by LC/MS-MS method	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)

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic parameters	At Day 4 and Day 11	Measures activated Partial Thromboplastin Time (aPTT)and measures ECarin Time (ECT),
Genotyping	At Day 1	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

Trial Locations

Locations (1)

Service de Medecine et Therapeutique; 🇫🇷 Saint-Etienne, France