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

NCT01199081 | Completed Phase 4 DMC

• 2 other identifiers: DRONE_C_046292010-019247-19
• Study Type: interventional
• Target: 154
• Locations: 7 countries
• Sites: 40

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

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (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 Outcomes (5)

• 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)

• Number of patients with AF recurrence

  From randomization up to 60 days after

• Number of patients with Adverse Events of Special Interest (AESIs)

  Up to 8 weeks after randomization

• Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest)

  Up to 8 weeks after randomization

• Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest)

  Up to 8 weeks after randomization

Study Arms (3)

Group A

EXPERIMENTAL

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

Group B

EXPERIMENTAL

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

Group C

EXPERIMENTAL

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

Interventions

Dronedarone DRUG

Pharmaceutical form: tablet Route of administration: oral (together with meal) Dose regimen: 400 mg twice daily

Also known as: Multaq®, SR33589

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (40)

Investigational Site Number 170001

Bogotá, Colombia

Location

Investigational Site Number 170002

Bucaramanga, Colombia

Location

Investigational Site Number 170003

Cartagena, Colombia

Location

Investigational Site Number 170006

Cartagena, Colombia

Location

Investigational Site Number 170007

Floridablanca, Colombia

Location

Investigational Site Number 170005

Medellín, Colombia

Location

Investigational Site Number 203005

Brno, Czechia

Location

Investigational Site Number 203003

Kladno, 27280, Czechia

Location

Investigational Site Number 203002

Olomouc, Czechia

Location

Investigational Site Number 203007

Prachatice, 38301, Czechia

Location

Investigational Site Number 203001

Prague, 12808, Czechia

Location

Investigational Site Number 203004

Prague, 19000, Czechia

Location

Investigational Site Number 203008

Příbram, 26101, Czechia

Location

Investigational Site Number 203006

Sternberk, 78501, Czechia

Location

Investigational Site Number 208-001

Aarhus, 8000, Denmark

Location

Investigational Site Number 208-002

Copenhagen, 2400, Denmark

Location

Investigational Site Number 208-003

København S, 2300, Denmark

Location

Investigational Site Number 250-004

Amiens, 80054, France

Location

Investigational Site Number 250-005

Boulogne-Billancourt, 92104, France

Location

Investigational Site Number 250-003

Chambray-lès-Tours, 37171, France

Location

Investigational Site Number 250-002

Grenoble, 38043, France

Location

Investigational Site Number 250-001

Montpellier, 34295, France

Location

Investigational Site Number 250-006

Toulouse, 31059, France

Location

Investigational Site Number 276-001

Bonn, 53105, Germany

Location

Investigational Site Number 276-002

Chemnitz, 09111, Germany

Location

Investigational Site Number 276-005

Hagen, 58095, Germany

Location

Investigational Site Number 276-003

Nuremberg, 90402, Germany

Location

Investigational Site Number 276-004

Wermsdorf, 04779, Germany

Location

Investigational Site Number 484003

Aguascalientes, 20020, Mexico

Location

Investigational Site Number 484002

México, 11340, Mexico

Location

Investigational Site Number 484001

San Luis Potosí City, 72244, Mexico

Location

Investigational Site Number 484005

San Luis Potosí City, 78200, Mexico

Location

Investigational Site Number 484004

Torreón, 27000, Mexico

Location

Investigational Site Number 484006

Zapopan, 45200, Mexico

Location

Investigational Site Number 724004

Barakaldo, 48903, Spain

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724005

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724002

Madrid, 28046, Spain

Location

Investigational Site Number 724003

Málaga, 29010, Spain

Location

Investigational Site Number 724006

Valdemoro, 28342, Spain

Location

Related Publications (1)

• 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.

  PMID: 32500725 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Dronedarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amiodarone; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 10, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: June 7, 2013

Record last verified: 2013-06

Locations

CZ (8); DE (5); DK (3); FR (6); CO (6); ME (6); ES (6)