Clinical trial NCT01199081: Pharmacokinetics and Optimal Timing of Dronedarone Initiation Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-09-10
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Plasma levels of dronedarone and its metabolite
timeFrame: 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:
measure: Plasma levels of amiodarone and its metabolite
timeFrame: At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose)
measure: Number of patients with AF recurrence
timeFrame: From randomization up to 60 days after
measure: Number of patients with Adverse Events of Special Interest (AESIs)
timeFrame: Up to 8 weeks after randomization
measure: Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest)
timeFrame: Up to 8 weeks after randomization
measure: Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest)
timeFrame: Up to 8 weeks after randomization
Other outcomes:
Locations:
city: Bogota
country: Colombia
facility: Investigational Site Number 170001
city: Bucaramanga
country: Colombia
facility: Investigational Site Number 170002
city: Cartagena
country: Colombia
facility: Investigational Site Number 170003
city: Cartagena
country: Colombia
facility: Investigational Site Number 170006
city: Floridablanca
country: Colombia
facility: Investigational Site Number 170007
city: Medellin
country: Colombia
facility: Investigational Site Number 170005
city: Brno
country: Czech Republic
facility: Investigational Site Number 203005
city: Kladno
country: Czech Republic
facility: Investigational Site Number 203003
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 203002
city: Prachatice
country: Czech Republic
facility: Investigational Site Number 203007
city: Praha 2
country: Czech Republic
facility: Investigational Site Number 203001
city: Praha 9
country: Czech Republic
facility: Investigational Site Number 203004
city: Pribram
country: Czech Republic
facility: Investigational Site Number 203008
city: Sternberk
country: Czech Republic
facility: Investigational Site Number 203006
city: Aarhus
country: Denmark
facility: Investigational Site Number 208-001
city: Copenhagen
country: Denmark
facility: Investigational Site Number 208-002
city: København S.
country: Denmark
facility: Investigational Site Number 208-003
city: AMIENS Cedex 1
country: France
facility: Investigational Site Number 250-004
city: Boulogne Billancourt Cedex
country: France
facility: Investigational Site Number 250-005
city: Chambray Les Tours Cedex
country: France
facility: Investigational Site Number 250-003
city: GRENOBLE cedex
country: France
facility: Investigational Site Number 250-002
city: Montpellier
country: France
facility: Investigational Site Number 250-001
city: TOULOUSE Cedex 9
country: France
facility: Investigational Site Number 250-006
city: Bonn
country: Germany
facility: Investigational Site Number 276-001
city: Chemnitz
country: Germany
facility: Investigational Site Number 276-002
city: Hagen
country: Germany
facility: Investigational Site Number 276-005
city: Nürnberg
country: Germany
facility: Investigational Site Number 276-003
city: Wermsdorf
country: Germany
facility: Investigational Site Number 276-004
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 484003
city: Mexico
country: Mexico
facility: Investigational Site Number 484002
city: San Luis Potosi
country: Mexico
facility: Investigational Site Number 484001
city: San Luis Potosi
country: Mexico
facility: Investigational Site Number 484005
city: Torreon
country: Mexico
facility: Investigational Site Number 484004
city: Zapopan
country: Mexico
facility: Investigational Site Number 484006
city: Barakaldo
country: Spain
facility: Investigational Site Number 724004
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724002
city: Málaga
country: Spain
facility: Investigational Site Number 724003
city: Valdemoro
country: Spain
facility: Investigational Site Number 724006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.