Safety and Efficacy of Vanoxerine for the Conversion of Subjects With Recent Onset Atrial Fibrillation or Flutter to Normal Sinus Rhythm (RESTORE SR)

RESTORE SR: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of a Single Oral Dose of Vanoxerine for The Conversion Of Subjects With REcent Onset Atrial Fibrillation or Flutter to Normal Sinus Rhythm

LGN-VN-003 is a prospective, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a single oral dose of vanoxerine for the conversion of subjects with recent onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm. Up to 625 subjects will be randomized in a 2:1 fashion so at least 400 vanoxerine and 200 placebo subjects receive study drug.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation or Flutter
• Intervention / Treatment: Drug: Placebo; Drug: Vanoxerine HCl

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
  • Sofia, Bulgaria
• Hungary
  • Budapest, Hungary
  • Hodmezovasarhely, Hungary
  • Pecs, Hungary
  • Rokus, Hungary
  • Zalaegerszeg, Hungary
• Israel
  • Ashkelon, Israel
  • Safed, Israel
• Russian Federation
  • Moscow, Russian Federation
  • Saint Petersburg, Russian Federation
  • Vladimir, Russian Federation
• United States
  • Colorado
    • Littleton, Colorado, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Iowa
    • Iowa City, Iowa, United States
  • Missouri
    • Saint Louis, Missouri, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
• Able to return for Day 8 follow up.
• Male or female 18 years of age or greater.
• Onset of AF/AFL within the 7 calendar days preceding randomization, based on symptoms.
• AF/AFL documented by ECG during the screening period.
• Adherence to local clinical standards or the ACC/AHA or ESC practice guidelines for AF/AFL regarding thromboembolic event prevention and treatment.

Exclusion Criteria:

• Previous exposure to vanoxerine HCl.
• Women of childbearing potential (neither surgically sterilized nor post-menopausal defined as cessation of menses for over one year)
• Systolic blood pressure <110 mmHg (unless documented to be usual value).
• Average heart rate <60 bpm documented by screening ECG.
• Average QTc >440 msec documented by screening ECG.
• QRS interval >140 msec documented by screening ECG.
• Paced atrial rhythm on screening ECG.
• History of receiving another Class I or Class III antiarrhythmic drug within 3 days prior to randomization. Excluded Class I antiarrhythmic drugs include quinidine, procainamide, disopyramide, lignocaine, mexilitine, flecainide, and propafenone. Excluded Class III drugs include dofetilide, sotalol, dronedarone, and ranolazine.
• History of amiodarone (oral or IV) within the 90 days prior to randomization.
• Native or prosthetic aortic or mitral stenosis with aortic valve area ≤1.0 cm2 or mitral valve area of <1.5 cm2 or any other valvular diseases for which surgery is indicated.
• Treatment with any loop diuretic (e.g., furosemide, bumetanide, torsemide, ethacrynic acid, etc.) in the 30 days prior to randomization.
• Ejection fraction of <35% within the 3 months prior to randomization (most recent measure if more than one).
• AF/AFL as a result of surgery (postoperative AF/AFL) within 30 days prior to randomization.
• History of electrical cardioversion within the 7 calendar days prior to randomization.
• History of any polymorphic ventricular tachycardia including torsades de pointes.
• History or family history of long QT syndrome or other inherited arrhythmia syndrome.
• History of ventricular tachycardia requiring drug or device therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vanoxerine HCl; Vanoxerine HCl, 400 mg (2 x 200 mg capsules), orally, single dose	Drug: Vanoxerine HCl
Placebo Comparator: Placebo; identically matching placebo capsules, orally, single-dose	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion to Sinus Rhythm	Conversion to sinus rhythm (or atrial paced rhythm in the case of subjects with a pacemaker and atrial leads) documented by ECG (Holter ECG, 12-lead ECG, monitor lead ECG, or other format ECG) of at least 1 continuous minute within the 24 hours defined by the time of study drug administration through 24 hours after the time of study drug administration.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of Stay (From Time of Study Drug Administration)	8 days

Collaborators and Investigators

• Sponsor: Laguna Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: August 23, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Vanoxerine
• Other Study ID Numbers: LGN-VN-003