Safety and Efficacy of Vanoxerine for Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm (COR-ART)

• ClinicalTrials.gov Identifier: NCT01691313
• Recruitment Status: Completed
• First Posted: September 24, 2012
• Results First Posted: December 22, 2015
• Last Update Posted: December 22, 2015
• Sponsor: Laguna Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Laguna Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Symptomatic Atrial Fibrillation; Atrial Flutter	Drug: Vanoxerine; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2012
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: vanoxerine 200mg; vanoxerine HCl 200mg single dose (2x 100 mg oral capsule)	Drug: Vanoxerine; single oral dose; Other Name: GBR12909
Placebo Comparator: placebo; placebo to match vanoxerine oral capsule	Drug: Placebo; single oral dose; Other Name: Placebo to match vanoxerine
Experimental: vanoxerine 300mg; vanoxerine HCl 300 mg single dose (3x 100mg oral capsules)	Drug: Vanoxerine; single oral dose; Other Name: GBR12909
Experimental: vanoxerine 400mg; vanoxerine HCl 400 mg single dose (4x 100 mg oral capsules)	Drug: Vanoxerine; single oral dose; Other Name: GBR12909

Outcome Measures

Primary Outcome Measures :

1. Conversion to Sinus Rhythm [ Time Frame: baseline through 4 hours ]
   proportion of subjects who convert to sinus rhythm through 4 hours after start of study drug
2. Conversion to Sinus Rhythm [ Time Frame: baseline through 24 hours ]
   proportion of subjects who convert to sinus rhythm through 24 hours after start of study drug

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Israel

Ashkelon, Israel

Haifa, Israel

Nazareth, Israel

Safed, Israel

Russian Federation

Moscow, Russian Federation

St Petersburg, Russian Federation

Sponsors and Collaborators

Laguna Pharmaceuticals, Inc.

Investigators

• Study Director: Howard C Dittrich, MD; ChanRx Corp.

More Information

Publications of Results:

Dittrich HC, Feld GK, Bahnson TD, Camm AJ, Golitsyn S, Katz A, Koontz JI, Kowey PR, Waldo AL, Brown AM. COR-ART: A multicenter, randomized, double-blind, placebo-controlled dose-ranging study to evaluate single oral doses of vanoxerine for conversion of recent-onset atrial fibrillation or flutter to normal sinus rhythm. Heart Rhythm. 2015 Jun;12(6):1105-12. doi: 10.1016/j.hrthm.2015.02.014. Epub 2015 Feb 12.

• Responsible Party: Laguna Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01691313
• Other Study ID Numbers: CRX-VN-002
• First Posted: September 24, 2012
• Results First Posted: December 22, 2015
• Last Update Posted: December 22, 2015
• Last Verified: November 2015

Keywords provided by Laguna Pharmaceuticals, Inc.:

vanoxerine; atrial fibrillation; atrial flutter; a-fib

Additional relevant MeSH terms:

Atrial Fibrillation; Atrial Flutter; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Vanoxerine; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs