Safety assessments
All subjects included were confined for 48-72 hours after drug administration. Recordings of adverse events, standard laboratory parameters (hematology, biochemistry and urinalysis), physical examination, vital signs, temperature and electronic 12 lead electrocardiograms (ECG) measurements (Cardioperfect, Welch Allyn, Rijswijk, The Netherlands) were performed at regular time points before and after dosing. In addition, from 30 minutes before dosing until 12 hours after dosing a continuous 1-lead ECG recording was performed (Nihon Kohden, Tokyo, Japan).