title: Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study.
abstract: OBJECTIVE
  Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers.
  
  
  METHODS
  In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI).
  
  
  RESULTS
  Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations.
  
  
  CONCLUSIONS
  Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA. john.edwards@frx.com
authors.forename: John
authors.initials: J
authors.lastname: Edwards
authors.forename: Vasi
authors.initials: V
authors.lastname: Sperry
authors.forename: Marijke H
authors.initials: MH
authors.lastname: Adams
authors.forename: Susan
authors.initials: S
authors.lastname: Gallipoli
authors.forename: Michael D
authors.initials: MD
authors.lastname: Thorn
authors.forename: James
authors.initials: J
authors.lastname: Longstreth
authors.forename: Ramesh
authors.initials: R
authors.lastname: Boinpally
mesh_terms: D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001572:Benzofurans / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010879:Piperazines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069503:Vilazodone Hydrochloride; D055815:Young Adult
chemical_list: D001572:Benzofurans; D007211:Indoles; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride