Official Title: “A Phase III Prospective, Randomized, Double-Blind, Active-Controlled, Multi-Center, Superiority Study of Vernakalant Injection Versus Amiodarone in Subjects With Recent Onset Atrial Fibrillation”

The primary objective of the study is to demonstrate the superiority of vernakalant injection over amiodarone injection in the conversion of atrial fibrillation (AF) to sinus rhythm (SR) within 90 minutes of the start of drug administration. The secondary objective is to compare the safety of vernakalant to amiodarone.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2009

This is a double-blind, active-controlled, double-dummy, multi-center, randomized trial in subjects with symptomatic AF of 3 to 48 hours duration. Subjects will be randomized to receive vernakalant injection or amiodarone injection in a 1:1 ratio.

Safety will be assessed through the monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests. At 2 hours after the start of infusion, electrical cardioversion may be performed or rate control medication may be administered. Class I and Class III antiarrhythmics are not to be administered for 24 hours after the start of infusion.

Subjects are to remain in the clinic for at least 6 hours after the start of infusion.

Subjects will attend a follow-up visit at 7 (±2) days after treatment and will receive a follow-up telephone call at 30 (±3) days for assessment of serious adverse events, concomitant medications related to serious adverse events, and recurrence of AF. All roles were blinded with the exception of each site's designated unblinded personnel who were responsible for randomization and preparation, dispensation and accountability of the study medication. Expanded Access was not available through this protocol.

Intervention(s) in this Clinical Trial

• Drug: Vernakalant Injection
  • 10-minute infusion of 3 mg/kg vernakalant injection followed by a 15-minute observation period, followed by an additional 10-minute infusion of 2 mg/kg of vernakalant if required (if the subject is still in AF).
• Drug: Amiodarone Injection:
  • 60-minute infusion of 5 mg/kg amiodarone followed by a maintenance infusion of 50 mg amiodarone over an additional 60 minutes (equivalent to approximately 15 mg/kg over 24 hrs).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Vernakalant Injection: In one infusion line, subjects will receive a 10-minute infusion of vernakalant followed by a 15-minute observation period, followed by an additional 10-minute infusion of vernakalant if required (if the subject is still in AF). To maintain blinding, a 60-minute infusion of placebo (D5W) will be administered in a second infusion line, followed by a maintenance infusion of placebo for a minimum of an additional 60 minutes.
• Active Comparator: 2
  • Amiodarone Injection: In one infusion line subjects will receive a 60-minute infusion of amiodarone followed by a maintenance infusion of amiodarone over an additional 60 minutes. To maintain blinding, a 10-minute infusion of placebo (normal saline) will be administered in a second infusion line, followed by a 15 minute observation period, followed by a 10 minute infusion of placebo if the subject is still in AF.

Primary Measures

• Proportion of subjects with conversion of atrial fibrillation to sinus rhythm within 90 minutes after the start of infusion.
  • Time Frame: Conversion of AF to SR for a minimum duration of one minute within 90 minutes after start of infusion.
    Safety Issue?: No

Secondary Measures

• Time to conversion within 90 minutes after the start of infusion.
  • Time Frame: Time to conversion of AF to SR within 90 minutes after start of infusion.
    Safety Issue?: No
• Proportion of subjects with symptom relief at 90 minutes after the start of infusion.
  • Time Frame: Relief of AF symptoms 90 minutes after start of infusion.
    Safety Issue?: No
• EQ-5D quality of life assessment.
  • Time Frame: Assessment of quality of life 2 hours after start of infusion.
    Safety Issue?: No
• Monitoring of adverse events, vital signs, continuous telemetry monitoring, 12-lead Holter monitoring, 12-lead ECGs, and laboratory tests.
  • Time Frame: Specified safety assessments completed at specified time points throughout the study from Screening to Discharge, at the Day 7 visit, and at the Day 30 follow-up call.
    Safety Issue?: Yes

Key Inclusion Criteria:

• Have symptomatic AF of 3 to 48 hours duration at baseline.
• Be eligible for cardioversion.
• Have adequate anticoagulation therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines [1].
• Be hemodynamically stable and have systolic blood pressure (BP) above 100 mmHg and less than 160 mmHg and diastolic BP less than 95 mmHg at screening and baseline.

Key Exclusion Criteria:

• Known or suspected prolonged QT or uncorrected QT interval of >440 msec as measured at screening on a 12 lead ECG, familial long QT syndrome, or previous torsades de pointes, ventricular fibrillation; or sustained ventricular tachycardia (VT).
• Symptomatic bradycardia, sick sinus syndrome, or ventricular rate less than 50 beats per minute (bpm) as documented by 12-lead ECG at screening.
• A QRS interval >140 msec.
• Atrial flutter.
• Significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis.
• Documented previous episodes of second or third degree atrioventricular (AV) block.
• Had a myocardial infarction (MI), acute coronary syndrome or cardiac surgery within 30 days prior to entry into the study.
• Uncorrected electrolyte imbalance of serum potassium or magnesium. Both K+ and Mg2+ must be corrected prior to dosing.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Cardiome Pharma

Overall Clinical Trial Officials and Contacts

Tomas Janota, MD Principal Investigator VFN III. interní klinika  

Overall Contact: Heather Kato, MAppSc 604-677-6905 hkato@cardiome.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00668759

Study ID Number: VERI-305-AMIO

ClinicalTrials.gov Identifier: NCT00668759

Health Authority: Canada: Health Canada