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

NCT ID: NCT01199081

Last Updated: 2013-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2012-04-30

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

Detailed Description

The maximum study duration per patient is 10 weeks

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dronedarone

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

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.

Group Type: EXPERIMENTAL

Dronedarone

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

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.

Group Type: EXPERIMENTAL

Dronedarone

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

Interventions

Dronedarone

Pharmaceutical form: tablet

Route of administration: oral (together with meal)

Dose regimen: 400 mg twice daily

Intervention Type: DRUG

Other Intervention Names

Multaq®; SR33589

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 170001

Bogotá, , Colombia

Investigational Site Number 170002

Bucaramanga, , Colombia

Investigational Site Number 170003

Cartagena, , Colombia

Investigational Site Number 170006

Cartagena, , Colombia

Investigational Site Number 170007

Floridablanca, , Colombia

Investigational Site Number 170005

Medellín, , Colombia

Investigational Site Number 203005

Brno, , Czechia

Investigational Site Number 203003

Kladno, , Czechia

Investigational Site Number 203002

Olomouc, , Czechia

Investigational Site Number 203007

Prachatice, , Czechia

Investigational Site Number 203001

Prague, , Czechia

Investigational Site Number 203004

Prague, , Czechia

Investigational Site Number 203008

Příbram, , Czechia

Investigational Site Number 203006

Sternberk, , Czechia

Investigational Site Number 208-001

Aarhus, , Denmark

Investigational Site Number 208-002

Copenhagen, , Denmark

Investigational Site Number 208-003

København S, , Denmark

Investigational Site Number 250-004

Amiens, , France

Investigational Site Number 250-005

Boulogne-Billancourt, , France

Investigational Site Number 250-003

Chambray-lès-Tours, , France

Investigational Site Number 250-002

Grenoble, , France

Investigational Site Number 250-001

Montpellier, , France

Investigational Site Number 250-006

Toulouse, , France

Investigational Site Number 276-001

Bonn, , Germany

Investigational Site Number 276-002

Chemnitz, , Germany

Investigational Site Number 276-005

Hagen, , Germany

Investigational Site Number 276-003

Nuremberg, , Germany

Investigational Site Number 276-004

Wermsdorf, , Germany

Investigational Site Number 484003

Aguascalientes, , Mexico

Investigational Site Number 484002

México, , Mexico

Investigational Site Number 484001

San Luis Potosí City, , Mexico

Investigational Site Number 484005

San Luis Potosí City, , Mexico

Investigational Site Number 484004

Torreón, , Mexico

Investigational Site Number 484006

Zapopan, , Mexico

Investigational Site Number 724004

Barakaldo, , Spain

Investigational Site Number 724001

Barcelona, , Spain

Investigational Site Number 724005

L'Hospitalet de Llobregat, , Spain

Investigational Site Number 724002

Madrid, , Spain

Investigational Site Number 724003

Málaga, , Spain

Investigational Site Number 724006

Valdemoro, , Spain

Countries

Colombia; Czechia; Denmark; France; Germany; Mexico; Spain

References

Naccarelli GV, Bhatt DL, Camm AJ, Le Heuzey JY, Lombardi F, Tamargo J, Martinez JM, Naditch-Brule L; ARTEMIS AF Investigators. Evaluation of the Switch From Amiodarone to Dronedarone in Patients With Atrial Fibrillation: Results of the ARTEMIS AF Studies. J Cardiovasc Pharmacol Ther. 2020 Sep;25(5):425-437. doi: 10.1177/1074248420926874. Epub 2020 Jun 5.

Reference Type: DERIVED

PMID: 32500725 (View on PubMed)

Other Identifiers

2010-019247-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRONE_C_04629

Identifier Type: -

Identifier Source: org_study_id