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

Phase 2

Completed

• Conditions: Symptomatic Atrial Fibrillation; Atrial Flutter
• Interventions: Drug: Vanoxerine; Drug: Placebo

• Registration Number: NCT01691313
• Lead Sponsor: Laguna Pharmaceuticals, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-09-20
• Study First Submitted QC: 2012-09-20
• Study First Posted: 2012-09-24
• Study Start: 2012-11
• Primary Completion: 2013-09
• Study Completion: 2013-10
• Results First Submitted: 2015-10-15
• Status Verified: 2015-11
• Results First Submitted QC: 2015-11-18
• Last Update Submitted: 2015-11-18
• Results First Posted: 2015-12-22
• Last Update Posted: 2015-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vanoxerine 200mg	Vanoxerine	vanoxerine HCl 200mg single dose (2x 100 mg oral capsule)
placebo	Placebo	placebo to match vanoxerine oral capsule
vanoxerine 300mg	Vanoxerine	vanoxerine HCl 300 mg single dose (3x 100mg oral capsules)
vanoxerine 400mg	Vanoxerine	vanoxerine HCl 400 mg single dose (4x 100 mg oral capsules)

Primary Outcome Measures

Name	Time	Method
Conversion to Sinus Rhythm	baseline through 24 hours	proportion of subjects who convert to sinus rhythm through 24 hours after start of study drug