Safety Study of Tecadenoson to Treat Atrial Fibrillation

An Open-Label, Sequential-Group, Dose-Escalation Study To Evaluate The Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous Tecadenoson Alone and in Combination With a Beta-Blocker in Adults With Rapid Atrial Fibrillation (CVT 4129)

Assess the tolerability and safety of a rapid bolus of tecadenoson at different dose levels when given alone and in combination with a beta-blocker (esmolol) in patients with atrial fibrillation to control rapid heart rate. Explore the pharmacokinetic and pharmacodynamic effects when given alone and in combination with beta-blocker (esmolol).

Inclusion Criteria:

• Have a diagnosis of atrial fibrillation in need of treatment for rate control
• Be able and willing to abstain from any antiarrhythmics, including atrioventricular (AV) nodal blocking agents (except for esmolol per protocol), from no later than 8:00 p.m. on the day prior to dosing until completion of the last dose period assessment
• Be able and willing to abstain from xanthine- or chocolate-containing foods, beverages, and medications
• Females must be post-menopausal or sterilized; or if of childbearing potential, must not be breastfeeding and must have a negative pregnancy test at screening and no intention of becoming pregnant during the course of the study. Males and females must be using adequate contraception during the study.

Exclusion Criteria:

• Have a known accessory pathway
• Have active myocardial ischemia or recent acute coronary syndrome
• Have acute or overt heart failure, bradycardia, heart block greater than first degree, or cardiogenic shock
• Have allergies or contraindications to treatment with esmolol or aminophylline, or any of their constituents
• Have a supine cuff systolic blood pressure < 90 mm Hg
• Be undergoing treatment with theophylline/aminophylline preparations, Trental® (pentoxifylline), or carbamazepine
• Have asthma or other reactive airways disease currently on-treatment
• Have a history of an active or chronic pancreatic disease or clinically significant increased levels of serum amylase or lipase