A Phase II/III Tolerance and Efficacy Study of RSD1235 in Patients With Atrial Flutter

There are approximately 2 million reported prevalent cases of atrial fibrillation and atrial flutter (AFL) in the United States (Heart Disease & Stroke Statistics - 2003 Update, AHA). These arrhythmias may be occasional or sustained. AF/AFL is usually associated with age, and general physical condition, rather than with a specific cardiac event, as is often the case with ventricular arrhythmia. While not directly fatal, these arrhythmias cause discomfort and can lead to stroke or congestive heart failure.

This Phase II/III trial is Cardiome's first study with RSD1235 for the treatment of atrial flutter. The study seeks to demonstrate RSD1235's abilities to convert AFL to sinus rhythm. The patient population will have atrial flutter of duration greater than 3 hours and less than or equal to 45 days.

This is a double-blind, placebo-controlled, randomized study in patients with AFL; stratification will be based on duration of AFL. 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.

Inclusion criteria

• 18 years of age or older.
• Have an atrial arrhythmia with dysrhythmic 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 s unless patient has pacemaker or uncorrected QT > 0.440 seconds as measured on a 12-lead ECG.
• Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to enrollment, or have previously received RSD1235.
• Have serious diseases/illnesses that could interfere with the conduct or validity of the study or compromise patient safety.
• Have received IV Class I or Class III antiarrhythmic drugs or IV amiodarone within 24 hours prior to dosing.