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

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT01199081
Collaborator
(none)
154
Enrollment
40
Locations
3
Arms
18
Duration (Months)
3.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The maximum study duration per patient is 10 weeks

Study Design

Study Type:
Interventional
Actual Enrollment :
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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.
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Apr 1, 2012
Actual Study Completion Date :
Apr 1, 2012

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Plasma levels of dronedarone and its metabolite [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

    1. Plasma levels of amiodarone and its metabolite [At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)]

    2. Number of patients with AF recurrence [From randomization up to 60 days after]

    3. Number of patients with Adverse Events of Special Interest (AESIs) [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)

    4. Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest) [Up to 8 weeks after randomization]

    5. Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest) [Up to 8 weeks after randomization]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Number 170001 Bogota Colombia
    2 Investigational Site Number 170002 Bucaramanga Colombia
    3 Investigational Site Number 170003 Cartagena Colombia
    4 Investigational Site Number 170006 Cartagena Colombia
    5 Investigational Site Number 170007 Floridablanca Colombia
    6 Investigational Site Number 170005 Medellin Colombia
    7 Investigational Site Number 203005 Brno Czech Republic
    8 Investigational Site Number 203003 Kladno Czech Republic 27280
    9 Investigational Site Number 203002 Olomouc Czech Republic
    10 Investigational Site Number 203007 Prachatice Czech Republic 38301
    11 Investigational Site Number 203001 Praha 2 Czech Republic 12808
    12 Investigational Site Number 203004 Praha 9 Czech Republic 19000
    13 Investigational Site Number 203008 Pribram Czech Republic 26101
    14 Investigational Site Number 203006 Sternberk Czech Republic 78501
    15 Investigational Site Number 208-001 Aarhus Denmark 8000
    16 Investigational Site Number 208-002 Copenhagen Denmark 2400
    17 Investigational Site Number 208-003 København S. Denmark 2300
    18 Investigational Site Number 250-004 AMIENS Cedex 1 France 80054
    19 Investigational Site Number 250-005 Boulogne Billancourt Cedex France 92104
    20 Investigational Site Number 250-003 Chambray Les Tours Cedex France 37171
    21 Investigational Site Number 250-002 GRENOBLE cedex France 38043
    22 Investigational Site Number 250-001 Montpellier France 34295
    23 Investigational Site Number 250-006 TOULOUSE Cedex 9 France 31059
    24 Investigational Site Number 276-001 Bonn Germany 53105
    25 Investigational Site Number 276-002 Chemnitz Germany 09111
    26 Investigational Site Number 276-005 Hagen Germany 58095
    27 Investigational Site Number 276-003 Nürnberg Germany 90402
    28 Investigational Site Number 276-004 Wermsdorf Germany 04779
    29 Investigational Site Number 484003 Aguascalientes Mexico 20020
    30 Investigational Site Number 484002 Mexico Mexico 11340
    31 Investigational Site Number 484001 San Luis Potosi Mexico 72244
    32 Investigational Site Number 484005 San Luis Potosi Mexico 78200
    33 Investigational Site Number 484004 Torreon Mexico 27000
    34 Investigational Site Number 484006 Zapopan Mexico 45200
    35 Investigational Site Number 724004 Barakaldo Spain 48903
    36 Investigational Site Number 724001 Barcelona Spain 08036
    37 Investigational Site Number 724005 Hospitalet de Llobregat Spain 08907
    38 Investigational Site Number 724002 Madrid Spain 28046
    39 Investigational Site Number 724003 Málaga Spain 29010
    40 Investigational Site Number 724006 Valdemoro Spain 28342

    Sponsors and Collaborators

    • Sanofi

    Investigators

    • Study Director: Clinical Sciences & Operations, Sanofi

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT01199081
    Other Study ID Numbers:
    • DRONE_C_04629
    • 2010-019247-19
    First Posted:
    Sep 10, 2010
    Last Update Posted:
    Jun 7, 2013
    Last Verified:
    Jun 1, 2013
    Additional relevant MeSH terms:
    Atrial Fibrillation
    Dronedarone

    Study Results

    No Results Posted as of Jun 7, 2013