Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study

Br J Clin Pharmacol. 2012 Feb;73(2):203-9. doi: 10.1111/j.1365-2125.2011.04088.x.


Aims: To assess steady-state effects of therapeutic and supra-therapeutic doses of prucalopride on the QT interval using a novel design involving a parallel placebo group with nested crossover for positive control.

Methods: A double-blind, double-dummy, placebo- and active-controlled study was conducted in 120 healthy male and female volunteers (NCT00903747). Volunteers were randomized to receive prucalopride 2-10 mg once daily (therapeutic and supratherapeutic doses, respectively) (group 1), placebo with 400 mg moxifloxacin on day 1 (group 2a), or placebo with moxifloxacin on day 15 (group 2b). Twelve-lead 24 h Holter ECGs recorded at various time-points were evaluated blind and centrally.

Results: Estimated mean difference in study specific corrected QT interval (QT(c)SS) time-matched change from baseline between prucalopride (2 and 10 mg) and placebo was <5 ms at all time points (maximum mean difference: 3.83 ms at 3.5 h post dose on day 5 with 2 mg [90% Cl -0.33, 6.38 ms]). Upper limits of the two-sided 90% CI for QT(c)SS were all <10 ms. There were no outlying QT(c)SS values >450 ms and no subjects had an increase >60 ms following prucalopride. Moxifloxacin produced the expected significant changes in QT(c)SS (>5 ms, maximum of +12.7 ms at 5 h post dose) at all time-points except 1 h post dose. Prucalopride resulted in small increases in heart rate (maximum of 5.8 beats min(-1)), which were similar for 2 and 10 mg. Prucalopride was well tolerated after first day of treatment.

Conclusion: Prucalopride at both therapeutic and supra therapeutic doses has no clinically significant effects on cardiac repolarisation in healthy volunteers.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Benzofurans / adverse effects
  • Benzofurans / pharmacology*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography / drug effects*
  • Female
  • Heart / drug effects*
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Serotonin 5-HT4 Receptor Agonists / adverse effects
  • Serotonin 5-HT4 Receptor Agonists / pharmacology*
  • Young Adult


  • Benzofurans
  • Serotonin 5-HT4 Receptor Agonists
  • prucalopride

Associated data