To Investigate the Effect of Intravenous Ondansetron on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects
Condition: Nausea and Vomiting, Chemotherapy-Induced
MeSH terms: Vomiting
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): ondansetron; moxifloxacin; saline
Intervention type(s): Drug; Drug; Other
Intervention description(s): FDA approved drug used to treat nausea and vomiting; FDA approved antibiotic commonly used as a positive control in thorough QT studies; USP saline IV solution used as placebo for ondansetron IV.
Other intervention name(s): Zofran; Avelox
Intervention MeSH terms: Moxifloxacin; Ondansetron
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: ondansetron; moxifloxacin; Zofran; thorough QT study; IV