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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: DRONEDARONE (SR33589); Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hiroshima-Shi, Japan
    • Investigational Site Number 392022
  • Kagoshima-Shi, Japan
    • Investigational Site Number 392018
  • Kasama-Shi, Japan
    • Investigational Site Number 392005
  • Kawanishi-Shi, Japan
    • Investigational Site Number 392014
  • Kawasaki-Shi, Japan
    • Investigational Site Number 392008
  • Kisarazu-Shi, Japan
    • Investigational Site Number 392007
  • Kobe-Shi, Japan
    • Investigational Site Number 392013
  • Kobe-Shi, Japan
    • Investigational Site Number 392012
  • Koriyama-Shi, Japan
    • Investigational Site Number 392003
  • Kurume-Shi, Japan
    • Investigational Site Number 392017
  • Miyazaki-Shi, Japan
    • Investigational Site Number 392023
  • Nagano-Shi, Japan
    • Investigational Site Number 392009
  • Nagasaki-Shi, Japan
    • Investigational Site Number 392019
  • Osaka-Shi, Japan
    • Investigational Site Number 392010
  • Sapporo-Shi, Japan
    • Investigational Site Number 392021
  • Sapporo-Shi, Japan
    • Investigational Site Number 392025
  • Sendai-Shi, Japan
    • Investigational Site Number 392002
  • Shirakawa-Shi, Japan
    • Investigational Site Number 392004
  • Shunan-Shi, Japan
    • Investigational Site Number 392016
  • Suwa-Shi, Japan
    • Investigational Site Number 392020
  • Takasaki-Shi, Japan
    • Investigational Site Number 392006
  • Tomakomai-Shi, Japan
    • Investigational Site Number 392001
  • Toshima-Ku, Japan
    • Investigational Site Number 392024
  • Ube-Shi, Japan
    • Investigational Site Number 392015
  • Yao-Shi, Japan
    • Investigational Site Number 392011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Estimate): October 16, 2013
• Last Update Submitted That Met QC Criteria: October 12, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anti-Arrhythmia Agents; Dronedarone
• Other Study ID Numbers: DRI10939; U1111-1116-9409 (Other Identifier: (UTN))