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: RESTORE SR.
Vanoxerine is an oral, 1,4-dialkylpiperazine derivative antiarrhythmic drug being evaluated for pharmacological cardioversion of atrial fibrillation (AF).



The purpose of this study was to evaluate the safety and efficacy of vanoxerine for the restoration of sinus rhythm in subjects with recent onset AF or atrial flutter (AFL).



RESTORE SR (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) was a prospective, multinational, randomized, double-blind, placebo-controlled trial that randomized subjects to a single oral dose of vanoxerine 400 mg or placebo (2:1 allocation).



A total of 41 subjects were randomized in the study (placebo [n = 15] and vanoxerine [n = 26]). The study was terminated prematurely because of safety concerns. Overall, 61% (23 of 38) of the treated cohort had a history of AF/AFL and 66% (27 of 41) had structural heart disease (SHD). The primary efficacy end point-conversion to sinus rhythm through 24 hours-occurred in 20% (3 of 15) in the placebo arm vs 69% (18 of 26) in the vanoxerine arm (P = .0024). The mean length of stay was 4.2 ± 2.9 days in the placebo arm vs 4.7 ± 3.2 days in the vanoxerine arm (P = .6561). The primary safety end point (all-cause death, ventricular fibrillation/tachycardia requiring intervention, or torsades de pointes) occurred in no patient in the placebo arm vs 11.5% (3 of 26) in the vanoxerine arm. All 3 patients had torsades de pointes and underlying SHD.



Vanoxerine is an oral, mixed ion channel blocker with IKr, INa, and L-type calcium channel activity. While oral therapy with 400 mg of vanoxerine appears effective for the termination of recent onset AF/AFL, its use was associated with a significant risk of ventricular proarrhythmia in patients with SHD.
Duke University, Durham, North Carolina. Electronic address: jonathan.piccini@duke.edu.
Jonathan P
JP
Piccini
Duke University, Durham, North Carolina.
Edward L C
EL
Pritchett
Momentum Research, Inc., Durham, North Carolina.
Beth A
BA
Davison
Momentum Research, Inc., Durham, North Carolina.
Gad
G
Cotter
University of North Carolina, Chapel Hill, North Carolina.
Laura E
LE
Wiener
University of North Carolina, Chapel Hill, North Carolina.
Gary
G
Koch
University of California, San Diego, California.
Gregory
G
Feld
Case Western Reserve University, Cleveland, Ohio.
Albert
A
Waldo
University Medical Center Groningen, Groningen, The Netherlands.
Isabelle C
IC
van Gelder
St George's University of London, London, United Kingdom.
A John
AJ
Camm
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.
Peter R
PR
Kowey
Laguna Pharmaceuticals, San Diego, California.
Julie
J
Iwashita
Laguna Pharmaceuticals, San Diego, California.
Howard C
HC
Dittrich
D000284:Administration, Oral; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001282:Atrial Flutter / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D017180:Tachycardia, Ventricular / Q000139:chemically induced*; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D010879:Piperazines; C043425:vanoxerine
Antiarrhythmic; Atrial fibrillation; Cardioversion; Clinical trial; Vanoxerine