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

Completed

Phase 3 Results

Trial Description

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.

Conditions

Interventions

  • Vernakalant hydrochloride Drug
    Intervention Desc: Vernakalant hydrochloride (RSD-1235) is a mixed ion channel blocker with selectivity for atrial ion channels that does not promote ventricular arrhythmia. An i.v. formulation is in development for acute conversion of patients with atrial fibrillation or atrial flutter, and an oral formulation is being developed for the maintenance of sinus rhythm in patients at risk of developing atrial fibrillation.
  • Vernakalant Injection 20 mg/mL Drug
    Other Names: RSD1235; Vernakalant; Vernakalant Injection; Vernakalant (iv)
    ARM 1: Kind: Experimental
    Label: 1
    Description: Atrial fibrillation (AF) duration of 3 hours to 7 days.
    ARM 2: Kind: Experimental
    Label: 2
    Description: AF duration of >7 days to <45 days

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated.

Outcomes

Type Measure Time Frame Safety Issue
Primary To demonstrate the effectiveness of RSD1235 in the conversion of atrial fibrillation to sinus rhythm.
Secondary To assess the safety of RSD1235 in this patient population.

Sponsors