• Boaz Mendzelevski, Jannie Ausma, Dennis O Chanter, Patricia Robinson, Rene Kerstens, Lieve Vandeplassche, and John Camm.
• CoreLab Partners Inc, London, UK.
• Br J Clin Pharmacol. 2012 Feb 1; 73 (2): 203-9.

AimsTo 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.MethodsA 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.ResultsEstimated 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.ConclusionPrucalopride at both therapeutic and supra therapeutic doses has no clinically significant effects on cardiac repolarisation in healthy volunteers.© 2011 SHIRE-MOVETIS NV. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

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