Dose Ranging Study of Dronedarone for the Control of Ventricular Rate in Japanese Patients With Permanent Atrial Fibrillation

Study Overview
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Brief Summary
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Primary Objective: - To assess the efficacy of dronedarone versus placebo for the control of ventricular rate in patients with permanent Atrial Fibrillation (AF). Secondary Objective: To assess the safety and tolerability of dronedarone after repeated oral doses of 300 mg, 400 mg, or 600 mg twice daily in the selected population. To document SR33589 and SR35021 trough plasma levels at steady state.

Detailed Description
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The study period per patient is approximatively 1 month broken down as follows: Screening period up to 7 days, Treatment period of 14 days, Follow-up period of 10 days.

Official Title
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Double Blind, Randomized, Placebo Controlled Dose Ranging Study of the Efficacy and Safety of Dronedarone (SR33589B) at 300, 400, or 600 mg BID for the Control of Ventricular Rate in Japanese Patients With Permanent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: DRONEDARONE (SR33589)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients of aged 20 years or more. Permanent Atrial Fibrillation [AF] (defined as duration of AF > 6 months) for which cardioversion is not considered and with resting ventricular heart rate ≥ 80 bpm at screening. Exclusion criteria: Unstable angina pectoris. History of torsades de pointes. Prolonged QT corrected interval (≥ 500 ms). Third degree atrioventricular block (AVB) on the screening ECG while in AF or, documentation on previous ECGs while in sinus rhythm of PR-interval > 0.28 sec or high degree AVB (2nd degree or higher) or, significant sinus node disease (documented pause ≥ 3 sec) - without a permanent pacemaker implanted. Congestive Heart Failure (CHF) of New York Heart Association classification (NYHA) class IV or recent (within 1 month prior to randomization) unstable NYHA class III. Treatment with other class I or III anti-arrhythmic drugs. Patients treated with amiodarone during the 4 weeks preceding randomization. Clinically relevant haematologic, hepatic, gastro-intestinal, renal, pulmonary, endocrinologic (in particular thyroid) or psychiatric disease. Hypokalemia and hypomagnesemia must be corrected before randomization. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dronedarone 300 mg<br>Dronedarone, 100mg + 200mg tablets twice daily, administered with food. | Drug: DRONEDARONE (SR33589)<br>* Pharmaceutical form: tablets Route of administration: oral<br>|
| Experimental: dronedarone 400 mg<br>Dronedarone, 400mg tablets twice daily, administered with food. | Drug: DRONEDARONE (SR33589)<br>* Pharmaceutical form: tablets Route of administration: oral<br>|
| Experimental: dronedarone 600 mg<br>Dronedarone, 400mg + 200mg tablets twice daily, administered with food. | Drug: DRONEDARONE (SR33589)<br>* Pharmaceutical form: tablets Route of administration: oral<br>|
| Placebo Comparator: placebo<br>Matching placebo tablets twice daily, administered with food. | Drug: placebo<br>* Pharmaceutical form: tablets Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean ventricular rate measured by 24-hour Holter Electrocardiogram (ECG) |  | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | up to 10 days after last drug intake | 
| Plasma trough concentrations for SR33589 |  | Day 14 | 
| Plasma trough concentrations for SR35021 |  | Day 14 |