Pharmacokinetics and Optimal Timing of Dronedarone Initiation Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation (ARTEMIS AF LT)
This study has been completed.
Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01199081
First received: September 9, 2010
Last updated: June 6, 2013
Last verified: June 2013
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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 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
| 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:
familial atrial fibrillation
MedlinePlus related topics:
Atrial Fibrillation
U.S. FDA Resources
Further study details as provided by Sanofi:
Primary Outcome Measures:
- Plasma levels of dronedarone and its metabolite [ Time Frame: At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose) ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Plasma levels of amiodarone and its metabolite [ Time Frame: At randomization (baseline), 3 hours after the first dose of dronedarone, after 1, 2 and 4 weeks of treatment with dronedarone (before dronedarone dose) ] [ Designated as safety issue: No ]
- Number of patients with AF recurrence [ Time Frame: From randomization up to 60 days after ] [ Designated as safety issue: No ]
- 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 alanine aminotransferase (ALT)
- Number of patients with symptomatic bradycardia (Heart Rate (HR) < 50 beats per minute at rest) [ Time Frame: Up to 8 weeks after randomization ] [ Designated as safety issue: Yes ]
- Number of patients with symptomatic tachycardia (HR > 120 beats per minute at rest) [ Time Frame: Up to 8 weeks after randomization ] [ Designated as safety issue: Yes ]
| Enrollment: | 154 |
| 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 (together with meal) Dose regimen: 400 mg twice daily Other Names:
|
|
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 (together with meal) Dose regimen: 400 mg twice daily Other Names:
|
|
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 (together with meal) Dose regimen: 400 mg twice daily Other Names:
|
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 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01199081
Show 40 Study Locations
Show 40 Study LocationsSponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
More Information
No publications provided
| Responsible Party: | Sanofi |
| 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: | June 6, 2013 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
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 June 18, 2013