Safety and Efficacy of Vanoxerine for Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm

Study Overview
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Brief Summary
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Evaluate the safety and efficacy of a single oral dose of vanoxerine compared to placebo, in a dose modification manner, on the conversion of symptomatic atrial fibrillation (a-fib) or flutter of recent onset to normal sinus rhythm.

Detailed Description
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Vanoxerine has important antiarrhythmic properties and may prove effective in converting AF/AFL to sinus rhythm in subjects with a history of AF. This is a prospective, randomized, double-blinded, placebo-controlled, dose-modifying study in subjects who have been in symptomatic AF or AFL for more than 3 hours and less than 7 days as dated by symptoms, who have AF/AFL documented on ECG at the time of study drug administration, and who satisfy the inclusion and exclusion criteria. The primary objectives of the trial are to evaluate the safety and efficacy of a single oral dose of vanoxerine compared to placebo following oral administration.

Official Title
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Randomized, Double-blind, Placebo-controlled Dose Modification Study to Evaluate the Safety and Efficacy of Single Doses of Vanoxerine for Conversion of Subjects With Recent Onset Atrial Fibrillation or Flutter to Normal Sinus Rhythm

Conditions
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Symptomatic Atrial Fibrillation, Atrial Flutter

Intervention / Treatment
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* Drug: Vanoxerine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: provide written informed consent, male or female 18 years of age or greater; women of child bearing potential must use adequate contraception symptomatic AF/AFL for more than 3 hours and less than 7 days (168 hours), as dated by symptoms AF/AFL documented by ECG at the start of study drug administration Exclusion Criteria: Systolic blood pressure <100 mmHg. Average heart rate <50 bpm. Average QTcF (Fridericia correction) >440 ms. Average QRS interval >140 ms. Paced atrial or ventricular rhythm on ECG. Serum potassium <3.5 meq/L (may be corrected prior to randomization). Received another intravenous Class I or Class III antiarrhythmic drug within prior 3 days. received amiodarone (oral or IV) in prior 3 months. Clinical evidence or history of acute coronary syndrome within 30 days prior to randomization. Aortic stenosis with aortic valve area equal to or less than 1.0 cm2. Rheumatic mitral stenosis with valve area of <1.5 cm2. Untreated hyperthyroidism. Acute pericarditis. AF/AFL as a result of surgery within the last 7 days History of failed electrical cardioversion History of polymorphic ventricular tachycardia (PVT, e.g. torsades de pointes). History or family history of long QT syndrome. History of ventricular tachycardia requiring drug or device therapy. History of NYHA Heart Failure Class 3 or 4 or recent (within 1 month) onset of heart failure not related to rapid ventricular response AF. Ejection fraction (EF) of 35% or less.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vanoxerine 200mg<br>vanoxerine HCl 200mg single dose (2x 100 mg oral capsule) | Drug: Vanoxerine<br>* single oral dose<br>* Other names: GBR12909;|
| Placebo Comparator: placebo<br>placebo to match vanoxerine oral capsule | Drug: Placebo<br>* single oral dose<br>* Other names: Placebo to match vanoxerine;|
| Experimental: vanoxerine 300mg<br>vanoxerine HCl 300 mg single dose (3x 100mg oral capsules) | Drug: Vanoxerine<br>* single oral dose<br>* Other names: GBR12909;|
| Experimental: vanoxerine 400mg<br>vanoxerine HCl 400 mg single dose (4x 100 mg oral capsules) | Drug: Vanoxerine<br>* single oral dose<br>* Other names: GBR12909;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion to Sinus Rhythm | proportion of subjects who convert to sinus rhythm through 4 hours after start of study drug | baseline through 4 hours | 
| Conversion to Sinus Rhythm | proportion of subjects who convert to sinus rhythm through 24 hours after start of study drug | baseline through 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vanoxerine, a-fib, atrial fibrillation, atrial flutter