Thorough QT study of the effect of fesoterodine on cardiac repolarization

Int J Clin Pharmacol Ther. 2010 May;48(5):309-18. doi: 10.5414/cpp48309.

Abstract

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.

Materials and 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / toxicity
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / therapeutic use
  • Benzhydryl Compounds / toxicity*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography*
  • Female
  • Fluoroquinolones
  • Humans
  • Least-Squares Analysis
  • Long QT Syndrome / chemically induced
  • Male
  • Middle Aged
  • Moxifloxacin
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / therapeutic use
  • Muscarinic Antagonists / toxicity*
  • Quinolines / toxicity
  • Urinary Bladder, Overactive / drug therapy

Substances

  • Aza Compounds
  • Benzhydryl Compounds
  • Fluoroquinolones
  • Muscarinic Antagonists
  • Quinolines
  • fesoterodine
  • Moxifloxacin