Thorough QT study of the effect of fesoterodine on cardiac repolarization.
OBJECTIVE
Fesoterodine 4 mg and 8 mg once daily are indicated for the treatment of overactive bladder. A thorough QT study was conducted to investigate the effects of fesoterodine on cardiac repolarization.


METHODS
In this parallel-group study, subjects were randomly assigned to receive double-blind fesoterodine 4 mg, fesoterodine 28 mg, or placebo or open-label moxifloxacin 400 mg (positive control) for 3 days. Electrocardiograms (ECGs) were obtained on Days -1 (baseline), 1, and 3. The primary analysis was the time-averaged changes from baseline for Fridericia's-corrected QT interval (QTcF) on Day 3.


RESULTS
Among 261 subjects randomized to fesoterodine 4 mg (n = 64), fesoterodine 28 mg (n = 68), placebo (n = 65), or moxifloxacin 400 mg (n = 64), 256 completed the trial. The least squares mean changes in QTcF from baseline were 21.1, 20.5, 18.5, and 31.3 ms (maximum), and -5.1, -4.2, -5.2, and 7.6 ms (time-averaged at Day 3) for placebo, fesoterodine 4 mg, fesoterodine 28 mg, and moxifloxacin, respectively. The lower limit of the 95% confidence interval exceeded 5 ms for moxifloxacin.


CONCLUSIONS
The results indicate that fesoterodine is not associated with QTc prolongation or other ECG abnormalities at either therapeutic or supratherapeutic doses.
Malhotra
B
B
Pfizer Inc, New York, NY 10017, USA. bimal.k.malhotra@pfizer.com
Wood
N
N
Sachse
R
R
Gandelman
K
K
D001372:Aza Compounds / Q000633:toxicity; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D016018:Least-Squares Analysis; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
D001372:Aza Compounds; D001559:Benzhydryl Compounds; D024841:Fluoroquinolones; D018727:Muscarinic Antagonists; D011804:Quinolines; C526675:fesoterodine; D000077266:Moxifloxacin