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document
Vilazodone lacks proarrhythmogenic potential in healthy participants : a thorough ECG study . 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 .
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Intervention_Pharmacological
Vilazodone
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Intervention_Pharmacological
Vilazodone
59245
Intervention_Pharmacological
vilazodone
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Intervention_Control
placebo-
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Intervention_Control
placebo
59248
Intervention_Pharmacological
moxifloxacin 400 mg
59249
Intervention_Pharmacological
vilazodone
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Intervention_Control
Placebo-corrected
59251
Intervention_Pharmacological
vilazodone
59252
Intervention_Pharmacological
vilazodone
59253
Intervention_Pharmacological
vilazodone
59254
Intervention_Pharmacological
Vilazodone
59255
Intervention_Pharmacological
vilazodone
59256
Intervention_Pharmacological
vilazodone
59257
Intervention_Pharmacological
moxifloxacin
59258
Intervention_Control
placebo
59259
Intervention_Pharmacological
Vilazodone
59260
Outcome_Physical
QT interval corrected for heart rate ( QTc )
59261
Outcome_Physical
QTcI duration
59262
Outcome_Physical
cardiac repolarization .
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Outcome_Physical
heart rate
59264
Outcome_Physical
PR
59265
Outcome_Physical
QRS interval duration
59266
Outcome_Physical
QTcI
59267
Outcome_Physical
QTc at Cmax
59268
Outcome_Adverse-effects
adverse events ( AEs )
59269
Outcome_Adverse-effects
AEs
59270
Outcome_Physical
cardiac repolarization
59271
Outcome_Physical
heart rate
59272
Outcome_Physical
PR
59273
Outcome_Physical
QRS interval duration
59274
Outcome_Physical
ECG morphology
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Participant_Condition
healthy volunteers .
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Participant_Condition
healthy adult participants .