The effect of propiverine on cardiac safety in healthy female subjects: a double-blind, placebo-controlled randomized study

Abstract

The influence of propiverine hydrochloride (p-HCL, Mictonorm®, Detrunorm®, Propinorm®, BUP-4®) on cardiac safety is currently under evaluation as latest in vitro results indicate a potential Ca2+-and K+-channel inhibitory property of p-HCL which may prolong myocardial repolarization (MR). The aim of the study was to assess potential effects of p-HCL on MR using QTc-interval, QT-dispersion and shape of T-wave as surrogate parameters in healthy female subjects, aged between 45-60 years. 24 healthy female subjects were enrolled and treated with p-HCL and placebo during two treatment periods of six days each (cross-over), separated by a washout period of at least 14 days. ECGs were recorded under strictly controlled resting conditions at predose, 1, 2, 4, 6, 8, 12 and 24 hrs post dose on days 1 and 6 and 7 days after the last intake of study medication, at corresponding time points, in each treatment period. Safety was assessed by investigation of ECGs, vital signs, clinical laboratory, adverse event monitoring (AEs), and physical examination (PE). Exploratory statistical analysis revealed no effect of p-HCL on myocardial repolarization in healthy women in comparison to placebo. There was no difference between p-HCL and placebo in QTc maximum in-crease, post-dose maximum of QTc, average QTc (over post-dose as-sessments up to 12 hours), rating of maximum QTc interval, rating of maximum in-crease of QTc interval, shape of T-wave, maximum increase of QT-dispersion and maximum decrease of QT-dispersion (P<.05). The present data revealed no effect of p-HCL on myocardial repolarization in healthy female subjects. It may therefore be concluded, that p-HCL does not raise concerns on cardiac safety in healthy subjects. P-HCL was well tolerated with respect to vital sings, clinical laboratory, AEs and PE. Acknowledgement: the study was kindly supported by an educational grant provided by Apogepha Arzneimittel GmbH.