PMID- 23611569
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20221207
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 51
IP  - 6
DP  - 2013 Jun
TI  - Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough 
      ECG study.
PG  - 456-65
LID - 10.5414/CP201826 [doi]
AB  - 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.
FAU - Edwards, John
AU  - Edwards J
AD  - Forest Research Institute, Jersey City, NJ, USA. john.edwards@frx.com
FAU - Sperry, Vasi
AU  - Sperry V
FAU - Adams, Marijke H
AU  - Adams MH
FAU - Gallipoli, Susan
AU  - Gallipoli S
FAU - Thorn, Michael D
AU  - Thorn MD
FAU - Longstreth, James
AU  - Longstreth J
FAU - Boinpally, Ramesh
AU  - Boinpally R
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Benzofurans)
RN  - 0 (Indoles)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin 5-HT1 Receptor Agonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - U8HTX2GK8J (Vilazodone Hydrochloride)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Arrhythmias, Cardiac/*chemically induced
MH  - Benzofurans/*adverse effects/pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Electrocardiography/*drug effects
MH  - Female
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Indoles/*adverse effects/pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Piperazines/*adverse effects/pharmacokinetics/pharmacology
MH  - Serotonin 5-HT1 Receptor Agonists/*adverse effects/pharmacokinetics/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/*adverse 
      effects/pharmacokinetics/pharmacology
MH  - Vilazodone Hydrochloride
MH  - Young Adult
EDAT- 2013/04/25 06:00
MHDA- 2013/08/07 06:00
CRDT- 2013/04/25 06:00
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/04/25 06:00 [entrez]
PHST- 2013/04/25 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
AID - 10576 [pii]
AID - 10.5414/CP201826 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2013 Jun;51(6):456-65. doi: 10.5414/CP201826.