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

Sponsor:	Sanofi-Aventis
Information provided by (Responsible Party):	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT01199081

Purpose

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 one month and two months after randomization
To assess the safety of the change from Amiodarone to Dronedarone and Dronedarone safety

Condition	Intervention	Phase
Atrial Fibrillation	Drug: DRONEDARONE	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: 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.

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Atrial Fibrillation

Drug Information available for: Amiodarone Amiodarone hydrochloride Dronedarone

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

Plasma levels of dronedarone and its metabolite [ Time Frame: First 4 weeks of treatment with Dronedarone ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Plasma levels of amiodarone and its metabolite [ Time Frame: First 4 weeks of treatment with Dronedarone ] [ Designated as safety issue: No ]
AF recurrence [ Time Frame: Up to 60 days after randomization ] [ Designated as safety issue: No ]
AF recurrence is documented by at least two consecutive scheduled or unscheduled 12-lead ECGs approximately 10 minutes apart and both showing AF
Number of patients with Adverse Events of Special Interest (AESIs) [ Time Frame: Up to 8 weeks after randomization ] [ Designated as safety issue: Yes ]
Specific AESIs are: congestive Heart Failure (CHF), Interstitial lung disease , severe skin disorders, peripheral neuropathy including optic neuropathy and increase in ALT
Symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest) and tachycardia (HR > 120 beats per minute at rest) [ Time Frame: Up to 8 weeks after randomization ] [ Designated as safety issue: Yes ]

Enrollment:	156
Study Start Date:	October 2010
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Dose regimen: 400 mg BID
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 Dose regimen: 400 mg BID
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 Dose regimen: 400 mg BID

Detailed Description:

The maximum study duration per patient is 10 weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 major amiodarone-related toxicity (interstitial lung disease, thyroid or hepatotoxicity)
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
Clinically overt congestive heart failure:
- with New York Heart Association (NYHA) class III or IV heart failure
- with LVEF < 35%
- or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic or
- 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
Clinically overt congestive heart failure:
- with New York Heart Association (NYHA) class III or IV heart failure
- with LVEF < 35%
- or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic or
- 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01199081

Show 40 Study Locations

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi-Aventis

More Information

No publications provided

Responsible Party:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT01199081 History of Changes
Other Study ID Numbers:	DRONE_C_04629, 2010-019247-19
Study First Received:	September 9, 2010
Last Updated:	April 20, 2012
Health Authority:	France: Afssaps - French Health Products Safety Agency

Additional relevant MeSH terms:

Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Anti-Arrhythmia Agents

Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on May 23, 2012