Abstract 15559: COR-ART: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose Modification Study to Evaluate Single Oral Doses of GBR-12909 for Conversion of Subjects With Atrial Fibrillation or Flutter of Recent Onset to Normal Sinus Rhythm
Purpose: To evaluate the safety and efficacy of a single oral dose of GBR-12909 (GBR) compared to placebo (PBO) in a dose modification manner in subjects with recent onset symptomatic atrial fibrillation (AF)/flutter (AFL).
Background: GBR is an investigational 1,4-dialkylpiperazine derivative with potent frequency dependent effects on IKr , ICaL and INa. In previous animal studies of AF/AFL, the drug demonstrated excellent efficacy for conversion to and maintenance of sinus rhythm with a low proarrhythmic potential.
Design: Cohorts of GBR and PBO subjects with recent (3 hours-7 days) onset symptomatic AF/AFL were enrolled beginning with a single dose of 200 mg, escalating or repeating based on safety and efficacy. Success was defined as conversion to sinus rhythm for at least 1 minute and was examined during 24 hours from time of study drug administration. Inpatient monitoring (including Holter) was performed for a minimum of 24 hours with a 7 day safety follow-up. Selected exclusion criteria included Class III/IV NYHA heart failure, EF < 35%, critical aortic or mitral valve stenosis, long QT, or recent rhythm control pharmacotherapy. Postoperative AF/AFL was not allowed although a history of prior AF/AFL was permitted.
Results: As of submission, 2 of the 3 planned cohorts have been randomized to 200 mg (N=22) and 300 mg (N=25) GBR, respectively (PBO=22). A third cohort (400 mg GBR) is currently being enrolled and those results will be available at study presentation.
Safety: Five of 22 (22.7%) PBO subjects reported 1 or more adverse events compared to 4 of 22 (18.2%) receiving 200 mg GBR and 2 of 25 (8%) receiving 300 mg GBR. Importantly, single oral doses of GBR were not associated with clinically significant bradyarrhythmia, heart block, ventricular proarrhythmia or organ toxicity.
Conclusion: Oral GBR-12909 was effective for conversion of recent onset, symptomatic AF/AFL, and, in this limited experience, was well tolerated.
- © 2013 by American Heart Association, Inc.