Pharmacokinetics and Optimal Timing of Dronedarone Initiation Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation (ARTEMIS AF LT)

June 6, 2013 updated by: Sanofi

A Randomized, International, Multi-center, Open-label Study to Document Pharmacokinetics and Optimal Timing of Initiation of Dronedarone Treatment Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation Whatever the Reason for the Change of Treatment.

Primary Objective:

- Explore Dronedarone and active metabolite pharmacokinetic (PK) profiles according to different timings of Dronedarone initiation.

Secondary Objective:

  • Explore potential PK interaction between Dronedarone and Amiodarone
  • Evaluate the rate of Atrial Fibrillation (AF) recurrence during the study period (from randomization up to 60 days after)
  • To assess the safety of the change from Amiodarone to Dronedarone and Dronedarone safety

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The maximum study duration per patient is 10 weeks

Study Type

Interventional

Enrollment (Actual)

154

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Colombia
      • Bogota, Colombia
        • Investigational Site Number 170001
      • Bucaramanga, Colombia
        • Investigational Site Number 170002
      • Cartagena, Colombia
        • Investigational Site Number 170003
      • Cartagena, Colombia
        • Investigational Site Number 170006
      • Floridablanca, Colombia
        • Investigational Site Number 170007
      • Medellin, Colombia
        • Investigational Site Number 170005
  • Czech Republic
      • Brno, Czech Republic
        • Investigational Site Number 203005
      • Kladno, Czech Republic, 27280
        • Investigational Site Number 203003
      • Olomouc, Czech Republic
        • Investigational Site Number 203002
      • Prachatice, Czech Republic, 38301
        • Investigational Site Number 203007
      • Praha 2, Czech Republic, 12808
        • Investigational Site Number 203001
      • Praha 9, Czech Republic, 19000
        • Investigational Site Number 203004
      • Pribram, Czech Republic, 26101
        • Investigational Site Number 203008
      • Sternberk, Czech Republic, 78501
        • Investigational Site Number 203006
  • Denmark
      • Aarhus, Denmark, 8000
        • Investigational Site Number 208-001
      • Copenhagen, Denmark, 2400
        • Investigational Site Number 208-002
      • København S., Denmark, 2300
        • Investigational Site Number 208-003
  • France
      • AMIENS Cedex 1, France, 80054
        • Investigational Site Number 250-004
      • Boulogne Billancourt Cedex, France, 92104
        • Investigational Site Number 250-005
      • Chambray Les Tours Cedex, France, 37171
        • Investigational Site Number 250-003
      • GRENOBLE cedex, France, 38043
        • Investigational Site Number 250-002
      • Montpellier, France, 34295
        • Investigational Site Number 250-001
      • TOULOUSE Cedex 9, France, 31059
        • Investigational Site Number 250-006
  • Germany
      • Bonn, Germany, 53105
        • Investigational Site Number 276-001
      • Chemnitz, Germany, 09111
        • Investigational Site Number 276-002
      • Hagen, Germany, 58095
        • Investigational Site Number 276-005
      • Nürnberg, Germany, 90402
        • Investigational Site Number 276-003
      • Wermsdorf, Germany, 04779
        • Investigational Site Number 276-004
  • Mexico
      • Aguascalientes, Mexico, 20020
        • Investigational Site Number 484003
      • Mexico, Mexico, 11340
        • Investigational Site Number 484002
      • San Luis Potosi, Mexico, 72244
        • Investigational Site Number 484001
      • San Luis Potosi, Mexico, 78200
        • Investigational Site Number 484005
      • Torreon, Mexico, 27000
        • Investigational Site Number 484004
      • Zapopan, Mexico, 45200
        • Investigational Site Number 484006
  • Spain
      • Barakaldo, Spain, 48903
        • Investigational Site Number 724004
      • Barcelona, Spain, 08036
        • Investigational Site Number 724001
      • Hospitalet de Llobregat, Spain, 08907
        • Investigational Site Number 724005
      • Madrid, Spain, 28046
        • Investigational Site Number 724002
      • Málaga, Spain, 29010
        • Investigational Site Number 724003
      • Valdemoro, Spain, 28342
        • Investigational Site Number 724006

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

Screening:

  • Paroxysmal or persistent AF having received at least 6 months of amiodarone before screening with at least the last 2 months at a regimen of 200 mg/day (during at least 5 days per week) prior to screening
  • Requiring a change from amiodarone treatment whatever the reason, but without liver, lung or thyroid toxicity related to previous use of amiodarone
  • At least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior cerebrovascular disease or left atrial diameter >= 50 mm
  • Effective anticoagulation treatments verified by International Normalized Ratio (INR) (target INR > 2)
  • QTc Bazett < 500 ms on 12-lead ECG

Randomization:

  • Outpatients and Inpatients (except patients hospitalized during screening period for SAE)
  • Sinus rhythm
  • Effective oral anticoagulation treatment verified by INR (target INR > 2). INR should be closely monitored after initiating dronedarone in patients taking vitamin K antagonist as per their label
  • QTc Bazett < 500 ms and PR < 280 ms on 12-lead ECG

Exclusion criteria:

Screening:

  • Contraindication to oral anticoagulation
  • Acute condition known to cause AF
  • Permanent AF
  • Bradycardia < 50 bpm at rest on the 12-lead ECG
  • History of, or current heart failure or left ventricular systolic dysfunction
  • Unstable hemodynamic conditions
  • Severe hepatic impairment
  • Wolff-Parkinson-White Syndrome
  • Previous catheter ablation for atrial fibrillation or catheter ablation scheduled in the next 10 weeks
  • Previous history of Amiodarone intolerance or toxicity
  • History of thyroid dysfunction

  • Mandatory contraindicated concomitant treatment:

    • potent cytochrome P450 (CYP3A4) inhibitors
    • drugs or herbal products that prolong the QT interval and known to increase the risk of Torsade de Pointes
  • Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) other than amiodarone if the anti-arrhythmic drug was taken less than one week before the day of screening (if taken more than one week before screening, the patient can be included)

Randomization

  • Bradycardia < 50 bpm on the 12-lead ECG
  • History of, or current heart failure or left ventricular systolic dysfunction
  • Unstable hemodynamic conditions
  • Severe hepatic impairment

  • Mandatory contraindicated concomitant treatment:

    • potent cytochrome P450 (CYP3A4) inhibitors
    • drugs or herbal products that prolong the QT interval and known to increase the risk of Torsade de Pointes

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A

Dronedarone 400 mg twice daily for 8 weeks starting from randomization.

The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.
Drug: Dronedarone

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

Other Names:
  • Multaq®
  • SR33589
Experimental: Group B

Dronedarone 400 mg twice daily for 6 weeks starting 2 weeks after randomization.

The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.
Drug: Dronedarone

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

Other Names:
  • Multaq®
  • SR33589
Experimental: Group C

Dronedarone 400 mg twice daily for 4 weeks starting 4 weeks after randomization.

The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.
Drug: Dronedarone

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

Other Names:
  • Multaq®
  • SR33589

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Plasma levels of dronedarone and its metabolite
Time Frame: At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)
At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma levels of amiodarone and its metabolite
Time Frame: At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)
At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)
Number of patients with AF recurrence
Time Frame: From randomization up to 60 days after
From randomization up to 60 days after
Number of patients with Adverse Events of Special Interest (AESIs)
Time Frame: Up to 8 weeks after randomization
Specific AESIs are: congestive Heart Failure (CHF), Interstitial lung disease , severe skin disorders, peripheral neuropathy including optic neuropathy and increase in alanine aminotransferase (ALT)
Up to 8 weeks after randomization
Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest)
Time Frame: Up to 8 weeks after randomization
Up to 8 weeks after randomization
Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest)
Time Frame: Up to 8 weeks after randomization
Up to 8 weeks after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

September 9, 2010

First Submitted That Met QC Criteria

September 9, 2010

First Posted (Estimate)

September 10, 2010

Study Record Updates

Last Update Posted (Estimate)

June 7, 2013

Last Update Submitted That Met QC Criteria

June 6, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DRONE_C_04629
  • 2010-019247-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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