10678
document
Tegaserod , a 5-hydroxytryptamine type 4 receptor partial agonist , is devoid of electrocardiographic effects . OBJECTIVES Certain GI prokinetic agents have been shown to affect cardiac repolarization , which may be associated with life-threatening arrhythmias . The selective 5-hydroxytryptamine type 4 receptor partial agonist tegaserod is a novel promotile agent developed for the treatment of functional motility disorders such as irritable bowel syndrome ( IBS ) . The aim of the study was to investigate the cardiac safety profile of tegaserod through analysis of electrocardiographic data from clinical studies conducted in patients with IBS and a study conducted in healthy male subjects . METHODS In three randomized , double blind , placebo-controlled , parallel group clinical studies , 2516 IBS patients with symptoms of abdominal pain and constipation received tegaserod 2 or 6 mg b.i.d . ( n = 1679 ) or placebo ( n = 837 ) for 12 wk . In an additional study , 36 healthy male subjects received iv . single doses of tegaserod ( 0.8 mg to 20 mg ) or placebo . Standard 12-lead electrocardiograms were recorded at baseline and during treatment . Baseline values were compared with data collected during the treatment period . RESULTS The proportion of patients with prolongation of the QTc interval was the same for placebo and tegaserod , as was the frequency of overall electrocardiographic abnormalities . No ventricular or supraventricular tachycardia was observed . Comparable electrocardiographic results were obtained during placebo and tegaserod treatment . In healthy volunteers , tegaserod at i.v . doses resulting in plasma concentrations up to 100 times those measured after therapeutic doses ( 6 mg b.i.d . ) did not influence electrocardiographic parameters . CONCLUSIONS Tegaserod is devoid of electrocardiographic effects and is not expected to adversely influence cardiac function . These data confirm preclinical findings .
10679
Intervention_Pharmacological
Tegaserod , a 5-hydroxytryptamine type 4 receptor partial agonist
10680
Intervention_Pharmacological
GI prokinetic agents
10681
Intervention_Pharmacological
selective 5-hydroxytryptamine type 4 receptor partial agonist tegaserod
10682
Intervention_Pharmacological
tegaserod
10683
Intervention_Pharmacological
tegaserod
10684
Intervention_Control
placebo
10685
Intervention_Pharmacological
tegaserod
10686
Intervention_Control
placebo
10687
Outcome_Physical
electrocardiographic effects
10688
Outcome_Other
cardiac safety profile
10689
Outcome_Physical
prolongation of the QTc interval
10690
Outcome_Physical
frequency of overall electrocardiographic abnormalities
10691
Outcome_Physical
ventricular or supraventricular tachycardia
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Outcome_Physical
electrocardiographic results
10693
Outcome_Physical
plasma concentrations
10694
Outcome_Physical
electrocardiographic effects
10695
Outcome_Physical
cardiac function
10696
Participant_Condition
IBS
10697
Participant_Condition
healthy
10698
Participant_Sex
male
10699
Participant_Sample-size
2516
10700
Participant_Condition
IBS
10701
Participant_Condition
abdominal pain
10702
Participant_Condition
constipation
10703
Participant_Sample-size
36
10704
Participant_Condition
healthy
10705
Participant_Sex
male
10706
Participant_Condition
healthy volunteers