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

Atrial Fibrillation Clinical Trial

— ARTEMIS AF LT  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01199081
• Other study ID #: DRONE_C_04629
• Secondary ID: 2010-019247-19
• Status: Completed
• Phase: Phase 4
• First received: September 9, 2010
• Last updated: June 6, 2013
• Start date: October 2010
• Est. completion date: April 2012

Study information

• Verified date: June 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

Description:

The maximum study duration per patient is 10 weeks

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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

Locations

Country	Name	City	State
Colombia	Investigational Site Number 170001	Bogota
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	Medellin
Czech Republic	Investigational Site Number 203005	Brno
Czech Republic	Investigational Site Number 203003	Kladno
Czech Republic	Investigational Site Number 203002	Olomouc
Czech Republic	Investigational Site Number 203007	Prachatice
Czech Republic	Investigational Site Number 203001	Praha 2
Czech Republic	Investigational Site Number 203004	Praha 9
Czech Republic	Investigational Site Number 203008	Pribram
Czech Republic	Investigational Site Number 203006	Sternberk
Denmark	Investigational Site Number 208-001	Aarhus
Denmark	Investigational Site Number 208-002	Copenhagen
Denmark	Investigational Site Number 208-003	København S.
France	Investigational Site Number 250-004	AMIENS Cedex 1
France	Investigational Site Number 250-005	Boulogne Billancourt Cedex
France	Investigational Site Number 250-003	Chambray Les Tours Cedex
France	Investigational Site Number 250-002	GRENOBLE cedex
France	Investigational Site Number 250-001	Montpellier
France	Investigational Site Number 250-006	TOULOUSE Cedex 9
Germany	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	Nürnberg
Germany	Investigational Site Number 276-004	Wermsdorf
Mexico	Investigational Site Number 484003	Aguascalientes
Mexico	Investigational Site Number 484002	Mexico
Mexico	Investigational Site Number 484001	San Luis Potosi
Mexico	Investigational Site Number 484005	San Luis Potosi
Mexico	Investigational Site Number 484004	Torreon
Mexico	Investigational Site Number 484006	Zapopan
Spain	Investigational Site Number 724004	Barakaldo
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724005	Hospitalet de Llobregat
Spain	Investigational Site Number 724002	Madrid
Spain	Investigational Site Number 724003	Málaga
Spain	Investigational Site Number 724006	Valdemoro

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Colombia,  Czech Republic,  Denmark,  France,  Germany,  Mexico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	Number of patients with AF recurrence		From randomization up to 60 days after	No
Secondary	Number of patients with Adverse Events of Special Interest (AESIs)	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	Yes
Secondary	Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest)		Up to 8 weeks after randomization	Yes
Secondary	Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest)		Up to 8 weeks after randomization	Yes