Safety Study of Tecadenoson to Treat Atrial Fibrillation

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Tecadenoson
* Drug: Esmolol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Period 1: 75 mcg, i.v. bolus. Period 2: 75 mcg, i.v. bolus + esmolol low dose infusion | Drug: Tecadenoson<br>* Tecadenoson administered intravenously (i.v.)<br>* Other names: CVT-510;Drug: Esmolol<br>* Esmolol low dose infusion according to manufacturer's instructions<br>* Other names: Brevibloc®;|
| Experimental: Cohort B<br>Period 1: 150 mcg, i.v. bolus. Period 2: 150 mcg, i.v. bolus + esmolol low dose infusion | Drug: Tecadenoson<br>* Tecadenoson administered intravenously (i.v.)<br>* Other names: CVT-510;Drug: Esmolol<br>* Esmolol low dose infusion according to manufacturer's instructions<br>* Other names: Brevibloc®;|
| Experimental: Cohort C<br>Period 1: 300 mcg, i.v. bolus. Period 2: 300 mcg, i.v. bolus + esmolol low dose infusion | Drug: Tecadenoson<br>* Tecadenoson administered intravenously (i.v.)<br>* Other names: CVT-510;Drug: Esmolol<br>* Esmolol low dose infusion according to manufacturer's instructions<br>* Other names: Brevibloc®;|
| Experimental: Cohort D<br>Period 1: 75 mcg, i.v. bolus. Period 2: 75 mcg, i.v. bolus + esmolol high dose infusion | Drug: Tecadenoson<br>* Tecadenoson administered intravenously (i.v.)<br>* Other names: CVT-510;Drug: Esmolol<br>* Esmolol low dose infusion according to manufacturer's instructions<br>* Other names: Brevibloc®;|
| Experimental: Cohort E<br>Period 1: 150 or 300 mcg, i.v. bolus. Period 2: 150 or 300 mcg, i.v. bolus + esmolol high dose infusion | Drug: Tecadenoson<br>* Tecadenoson administered intravenously (i.v.)<br>* Other names: CVT-510;Drug: Esmolol<br>* Esmolol low dose infusion according to manufacturer's instructions<br>* Other names: Brevibloc®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities |  | Baseline to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiac parameters R-R interval and ventricular rate measured by electrocardiogram |  | Baseline to Day 7 |