Absence of QT prolongation after administration of a 24-mg bimodal-release ondansetron pill (RHB-102).

Prospective data evaluating the effect of ondansetron on the corrected QT (QTc) interval is lacking in emergency department clinical use. As part of a randomized trial of a 24-mg bimodal-release ondansetron (RHB-102) pill, we tested the effect of RHB-102 compared to placebo on QTc change. This was a planned safety outcome analysis within a multicenter, double-blind, placebo-controlled trial. The trial compared the effects of RHB-102 among patients ≥12 years who presented to 21 centers with symptoms of acute gastroenteritis. Patients with an initial baseline electrocardiogram as well as a follow-up electrocardiogram 4 h later were included in the analysis. The safety endpoint for this analysis was the change from baseline in QTc interval at 4 h, the median time at which ondansetron serum level peaks. A total of 147 patients were included with a mean baseline QTc in the RHB-102 and placebo arms of 410 and 406 ms, respectively. There was no difference in the change in QTc at 4 h post-study drug administration between the RHB-102 (+4, 95% CI 1-8 ms) and placebo group (+5, 95% CI 1-9 ms). In the RHB-102 arm, 6.6% of patients had a QTc change >30 ms and in the placebo arm 3.6% (p = 0.48). No patient in either arm had a QTc change >60 ms after study drug administration. In patients with normal baseline QTc, 24-mg bimodal-release ondansetron did not prolong the QTc in comparison to placebo.

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Déclaration de conflit d'intérêts

Declaration of competing interest Grant money for commercial research: JM, SH, LL, AM, BH, JA, and RS report grant money to their institutions from RedHill Biopharma for the performance of this trial. Employment: TP, RS, IK, and RF are employed by RedHill Biopharma, which manufacturers a product related to the subject matter.