A single-blind, randomized, five-way cross-over, safety and tolerability trial was conducted to determine whether intravenous (i.v.) dolasetron mesylate at varying single doses induces changes in ECG intervals in healthy volunteers and to compare these changes with a single intravenous dose of ondansetron or placebo. Thirty healthy male volunteers received 1.2, 1.8, and 2.4 mg/kg i.v. dolasetron mesylate, 32 mg i.v. ondansetron, and placebo on 5 separate days. ECGs were recorded at intervals during the 24 h after study drug administration. The changes in ECG intervals observed after dolasetron mesylate or ondansetron were acute, transient, and asymptomatic. Dolasetron mesylate resulted in slight but statistically significant dose-related increases in heart rate (HR) and PR and QRS intervals (between h 0 and 4). A statistically significant increase in QTc interval was detected with both dolasetron mesylate (2.4 mg/kg) and ondansetron. Ondansetron also produced a slight but statistically significant increase in JT interval and a decrease in HR. These changes in ECG intervals were usually observed between h 0 and 4; all parameters returned to baseline within 8 h of treatment. The results demonstrate that both dolasetron mesylate and ondansetron prolong the QTc interval. However, dolasetron mesylate predominantly altered ECG parameters indicative of ventricular depolarization (QRS duration), whereas ondansetron predominantly affected ventricular repolarization as measured by a prolongation in the JT interval. Both dolasetron and ondansetron were well tolerated. The adverse event (AE) rate was 13.3% (4 of 30); all AE were of mild or moderate severity and were distributed across all dose arms.

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