title: Effect of single doses of IV palonosetron, up to 2.25 mg, on the QTc interval duration: a double-blind, randomized, parallel group study in healthy volunteers.
abstract: OBJECTIVE
  The use of serotonin type 3 (5-HT3) receptor antagonists (RAs) in the prevention of nausea and vomiting caused by emetogenic chemotherapy is part of a comprehensive management strategy for patients undergoing chemotherapy. Electrocardiographic effects have been reported in patients after intravenous administration of 5-HT3 RAs. The present study investigated the electrocardiogram (ECG) profile of the 5-HT3 RA palonosetron following International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E14 Guidelines.
  
  
  METHODS
  A total of 221 healthy subjects (101 females, 120 males) were randomized in this phase I, double-blind, double-dummy, parallel group study and assigned to one of five treatments: placebo, palonosetron (0.25, 0.75, or 2.25 mg), or moxifloxacin (400 mg). ECGs were recorded for 24 h pre-dosing until 48 h post-dose. The primary endpoint was the placebo time-matched and baseline-subtracted individual QTc interval prolongation (ΔΔQTcI).
  
  
  RESULTS
  The QTc interval was not prolonged after administration of palonosetron (ΔΔQTcI upper confidence interval was <10 ms for all time points in all palonosetron treatment groups). Assay sensitivity was confirmed with the expected change in the QTc interval after administration of the positive control moxifloxacin.
  
  
  CONCLUSIONS
  Palonosetron, even at supratherapeutic doses, has no effect on cardiac repolarization as measured by the QTc interval in a validated controlled clinical trial.
authors.affiliation: eResearchTechnology Inc., Philadelphia, PA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
authors.affiliation: KF Consulting LLC, Fort Myers, FL, USA.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Flaharty
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland. Simona.Parisi@helsinn.com.
authors.forename: Simona
authors.initials: S
authors.lastname: Parisi
authors.affiliation: Helsinn Healthcare SA, Lugano, Switzerland.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Moresino
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects; D012016:Reference Values; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007546:Isoquinolines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D000077924:Palonosetron
keywords: 5-HT3 receptor antagonists; Chemotherapy-induced nausea and vomiting; Palonosetron; QTc interval