Phase III Tolerance and Efficacy Study of RSD1235 in Patients With Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
This study is being conducted to demonstrate the effectiveness of RSD1235 in the conversion of atrial fibrillation to sinus rhythm.

Detailed Description
-----------------
There are approximately 2 million reported prevalent cases of atrial fibrillation (AF) and atrial flutter in the United States (Heart Disease & Stroke Statistics - 2003 Update, AHA). These arrhythmias may be occasional or sustained. While not directly fatal, these arrhythmias cause discomfort and can lead to stroke or congestive heart failure. This Phase III trial is Cardiome's first pivotal study with RSD1235. The study seeks to confirm the findings of the Phase II proof-of-concept through demonstration of RSD1235's abilities to convert AF to sinus rhythm. The patient population will include recent onset AF (AF duration of 3 hours to 7 days) and patients with longer AF duration. This is a double-blind, placebo-controlled, randomized study in patients with AF; stratification will be based on duration of AF. Treatment will be considered successful if there is a treatment-induced conversion of atrial arrhythmia to sinus rhythm for a minimum of 1-minute by Hour 1.5 (Time 0 = start of first infusion). All patients will be evaluated for safety.

Official Title
-----------------
A Phase III Prospective, Randomized, Double-Blind, Placebo-Controlled, Multi-Centred Tolerance and Efficacy Study of RSD1235 in Patients With Atrial Fibrillation

Conditions
-----------------
Atrial Fibrillation

Intervention / Treatment
-----------------
* Drug: Vernakalant Injection 20 mg/mL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older; Have an atrial arrhythmia with symptoms that has been sustained for greater than 3 hours and up to 45 days. Have adequate anticoagulant therapy. Exclusion Criteria: Have a QRS > 0.14 seconds unless patient has pacemaker or uncorrected QT > 0.440 seconds as measured on a 12-lead ECG. Have serious diseases/illnesses that could interfere with the conduct or validity of the study or compromise patient safety. Have received intravenous Class I or Class III antiarrhythmic drugs or intravenous amiodarone within 24 hours prior to dosing.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Atrial fibrillation (AF) duration of 3 hours to 7 days. | Drug: Vernakalant Injection 20 mg/mL<br> <br> * Other names: RSD1235; Vernakalant; Vernakalant Injection; Vernakalant (iv);|
| Experimental: 2<br>AF duration of >7 days to <45 days | Drug: Vernakalant Injection 20 mg/mL<br> <br> * Other names: RSD1235; Vernakalant; Vernakalant Injection; Vernakalant (iv);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate the effectiveness of RSD1235 in the conversion of atrial fibrillation to sinus rhythm. |  | The proportion of patients with atrial fibrillation (AF) of 3 hours to 7 days duration who have treatment-induced conversion of AF to sinus rhythm for a minimum duration of one minute in the first 90 minutes after the first exposure to study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of RSD1235 in this patient population. |  | The proportion of patients with AF of 3 hours to 45 days duration who have treatment-induced conversion of AF to sinus rhythm for a minimum duration of one minute in the first 90 minutes after the first exposure to study treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atrial fibrillation, RSD1235, Atrial fibrillation of 3 hours to 7 days duration., Atrial fibrillation of 3 hours to 45 days duration.