NCT01449188

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

A Randomized, Double-blind, Four-period Crossover Study to Investigate the Effect of Intravenous Ondansetron, a 5-HT3 Antagonist, on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Ondansetron, also known as Zofran, is a marketed compound used for the prevention of nausea and vomiting. This study, called a thorough QT study, will characterize the effects of a single intravenous (IV) dose of ondansetron on cardiac repolarization as compared to placebo. Moxifloxacin, a commercially available antibiotic known to cause a mild QT prolongation, will be used as a positive control and will be given orally. The cardiac repolarization will be measured by taking consecutive ECGs on a recording device known as a Holter monitor and measuring the QT interval at specified times. In addition, blood samples will also be taken at specified times and will be used to measure the amount of study medication in the body.

Detailed description

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.

Conditions

• Nausea and Vomiting, Chemotherapy-Induced

Interventions

Type	Name	Description
DRUG	ondansetron	FDA approved drug used to treat nausea and vomiting
DRUG	moxifloxacin	FDA approved antibiotic commonly used as a positive control in thorough QT studies
OTHER	saline	USP saline IV solution used as placebo for ondansetron IV.

Timeline

• Start date: 2011-08-16
• Primary completion: 2011-12-19
• Completion: 2011-12-19
• First posted: 2011-10-10
• Last updated: 2017-11-13

Locations

1 site across 1 country: United States