To Investigate the Effect of Intravenous Ondansetron on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects

Ondansetron was first approved in 1991 for treatment of nausea and vomiting associated with chemotherapy and surgical procedures and as ondansetron was developed prior to current regulatory requirements, a formal, thorough QT study has not been performed for this compound. The purpose of this study is to further define the safety of ondansetron as some effects on QT interval prolongation have been observed for this and other members of the 5-HT3 inhibitor class of compounds. In the case of ondansetron, these effects have been rare and transient and noted primarily with IV administration, however, the extent to which ondansetron prolongs the QT interval has not been defined. This study will quantify the effects of a single dose of IV ondansetron administered over 15 minutes on cardiac conduction in a double-blind, cross-over study and compared to placebo and a positive control, oral moxifloxacin. Pre- and post-dose digital electrocardiograms (ECGs) will be obtained by continuous Holter monitoring (1000 Hz) for blinded over-read by a third party vendor. This double-blind study will randomize approximately 60 healthy adult male and female volunteers to one of 12 sequences each consisting of 4 study treatment periods in a crossover design with a 7-day washout between each treatment period. Subjects will receive placebo, moxifloxacin (single 400 mg tablet), ondansetron 8 mg, and ondansetron 32 mg based on the randomized sequence. Both ondansetron and the placebo for ondansetron will be administered intravenously over 15 minutes. Moxifloxacin, a drug known to cause mild QTc prolongation, is included as a positive control and will be dosed as open label. Serial blood samples will be obtained to determine ondansetron and, if needed, moxifloxacin pharmacokinetic parameters. Safety and tolerability will be assessed through physical exams, adverse events, concurrent medications, clinical laboratory tests and vital signs.