Antiarrhythmic and Symptomatic Effect of ISIS CRP Rx Targeting CRP in Paroxysmal Atrial Fibrillation

Inclusion criteria

• Male of female; age over 18 years
• Dual chamber permanent pacemaker implanted
• Confirmed diagnosis of paroxysmal atrial fibrillation with an AF burden of 1 to 50%, as derived from pacemaker diagnostic algorithms
• Able to have pacemaker antiarrhythmic algorithms turned off for the duration of the study
• Able to discontinue all Class I and III antiarrhythmic medication for the duration of the study
• Therapeutically anticoagulated with warfarin or dabigatran, and anticipated to be for duration of the study
• High sensitivity C-Reactive Protein (hsCRP) between 2 and 10 mg/L (inclusive)

Exclusion criteria

• Clinically significant abnormalities in medical history, physical examination, or screening laboratory results that would render a subject unsuitable for inclusion
• NYHA class III/IV heart failure
• Impaired left ventricular function of less than 45% determined by echocardiography within 3 months of screening
• Moderate or greater mitral regurgitation assessed by echocardiography within 3 months of screening
• Permanent AF
• Continuous Amiodarone therapy within 90 days prior to Study Day 1
• Treatment with another Study Drug, biological agent, or device within one-month of screening, or five half-lives of study agent, whichever is longer
• Use of systemic corticosteroids or other anti-inflammatory medications including non-steroidal anti-inflammatory drugs (NSAIDs)
• Use of statins, ACE inhibitors or AT-receptor antagonists unless on a stable regimen for at least 3 months prior to dosing and will remain on a stable regimen for the duration of the study
• Uncontrolled hypertension (BP >160/100)
• Current or expected use of any anticoagulant apart from warfarin or dabigatran