Title

A 24 Milligram Bimodal Release Ondansetron Pill (RHB-102) Shows No Evidence of QT Interval Prolongation

Document Type

Conference Proceeding

Publication Date

2018

Publication Title

Acad Emerg Med

Abstract

Background: Ondansetron is first line treatment for vomiting and one of the most common medications in the ED setting. Concerns over the 32mg IV dose association with prolonged corrected QT interval (QTc) and torsades de pointes prompted an FDA warning in 2011. Still, there is a paucity of prospective data evaluating lower dose ondansetron in the acute care setting. As part of a double blind, placebo-controlled trial of a 24 mg bimodal release ondansetron (BRO) pill, we tested the safety of BRO compared to placebo on QTc change. The safety outcomes included either an increase in mean QTc or an increase in the proportion of patients with QTc change > 30 msec.

Methods: This was a planned safety outcome analysis within a multi-center, double blind, placebo-controlled trial. The trial compared the effects of BRO among patients â%o¥ 12 years, who presented to 19 EDs and 2 urgent-care centers with symptoms of acute gastroenteritis. The BRO provides early serum levels similar to an 8mg immediate release ondansetron tablet with sustained levels over 24 hours. Exclusion criteria were CHF, uncontrolled diabetes, recent surgery, alcohol and substance abuse, and a baseline EKG QTc> 450ms. The safety endpoint for this analysis was the change in QTc interval at 4 hours following administration of study drug compared to baseline QTc. We calculated each QTc using both Bazett’s (QTcB) and Fredericia’s (QTcF) formulas. Statistical analyses included Chi Square and student’s t-test methods.

Results: There were 156 patients who had ECG testing within the overall trial. The mean baseline QTcB in the BRO and placebo arms were 429.9 and 423.5 msec respectively. There was no difference in the change in QTcB at 4 hours post-study drug administration between the BRO (+1.1, 95% CI -2.9 to 5.2 msec) and placebo group (+4.4, 95% CI -0.2 to 9.0 msec). There was similarly no difference using the QTcF calculation. There were 4 (4.4%) patients in the BRO arm with a QTcB change > 30 msec vs. 4 (7.1%) in the placebo arm (p=0.48). No patients in either arm had a QTcB change > 60 msec after study drug administration.

Conclusion: In patients with normal baseline QTc, bimodal extended release ondansetron caused no QTc prolongation in comparison to placebo. This supports previous post-marketing safety data for the currently available single dose short-acting oral formulation among patients without risk factors.

Volume

25

First Page

S27

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