NCT01385683

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Jun 2011

Typical duration for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
26 days until next milestone

First Submitted

Initial submission to the registry

June 27, 2011

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 30, 2011

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2011

Completed
Last Updated

March 22, 2012

Status Verified

March 1, 2012

Enrollment Period

6 months

First QC Date

June 27, 2011

Last Update Submit

March 21, 2012

Conditions

Healthy

Keywords

Healthy volunteerPharmacokineticpharmacodynamicPolymorphism, Genetic

Outcome Measures

Primary Outcomes (1)

  • 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)

    At Day 4 and Day 11

Secondary Outcomes (2)

  • Pharmacodynamic parameters

    At Day 4 and Day 11

  • Genotyping

    At Day 1

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Dabigatran then dabigatran and clarithromycin

Drug: Dabigatran then dabigatran and clarithromycin

Arm B

ACTIVE COMPARATOR

Clarithromycin and dabigatran and dabigatran

Drug: Clarithromycin and dabigatran then dabigatran

Interventions

Dabigatran then dabigatran and clarithromycinDRUG

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)

Also known as: Dabigatran (Pradaxa)75 mg, Clarithromycin (Zeclar) 500 mg
Arm A
Clarithromycin and dabigatran then dabigatranDRUG

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.

Also known as: Dabigatran (Pradaxa) 75 mg, Clarithromycin (Zeclar) 500 mg
Arm B

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Service de Medecine et Therapeutique

Saint-Etienne, 42055, France

Location

MeSH Terms

Interventions

ClarithromycinDabigatran

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Patrick MISMETTI, MD PhD

    CHU de Saint-Etienne

    PRINCIPAL INVESTIGATOR

  • Xavier DELAVENNE, Pharmacist

    CHU de Saint-Etienne

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2011

First Posted

June 30, 2011

Study Start

June 1, 2011

Primary Completion

December 1, 2011

Study Completion

December 1, 2011

Last Updated

March 22, 2012

Record last verified: 2012-03

Locations

FR(1)