Twelve-lead electrocardiography (ECG) was taken at screening and subjects with ECG findings, such as QTc interval using Fridericia’s formula (QTcF) over 450 ms, PR interval

above 200 ms or below 110 ms, intraventricular conduction delay with QRS over 120 ms, second- or third-degree atrioventricular block, pathologic Ruboxistaurin supplier Q waves (defined as Q-wave over 40 ms or depth over 0.5 mV), ventricular preexcitation, and left or right bundle branch block, were excluded from the study. Subjects with the following criteria were also excluded: family history of long QT syndrome, any torsades de pointes risk factors, such as sudden death, cardiac failure, hypokalemia, and arrhythmia, and history of hypersensitivity to drugs, including quinolone antibiotics. Enrolled subjects were asked not to drink alcohol or caffeinated beverages and not to smoke from 24 h prior to hospitalization until the end of the study. 2.2 Study Design This study was designed as a multi-center, randomized, open-label, placebo-controlled, three-way crossover trial. Eligible subjects were randomized into six sequences (Fig. 1). Fig. 1 Study design pharmacokinetic sampling (black shaded line); 12-lead electrocardiogram MRT67307 mouse (grey shaded line) On day 1, baseline 12-lead ECGs were find more measured after 10 min of supine position using either

MAC5000 or MAC5500 (GE Healthcare, Milwaukee, WI, USA; set at 25 mm/s) at the following time points: 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24 h. ECGs were recorded once for every time point. On day 2, subjects received one of the three treatments in each period according to their sequence group: placebo (water), moxifloxacin 400 mg (Avelox Tablets, Bayer Korea Ltd., Seoul, Korea), or moxifloxacin 800 mg. ECGs were then recorded at the corresponding time points in the same manner as on the baseline day. Blood sampling for the pharmacokinetic (PK) analyses was conducted at the same time points as the ECG recordings

for subjects who took moxifloxacin. When the procedures were to be processed at the same time, the ECG was taken first, after which point, the vital signs were measured Epothilone B (EPO906, Patupilone) and the PK sampling was conducted to minimize the influence of the other procedures on the ECG results. The plasma was immediately separated by centrifugation at 2,093×g for 10 min at 4 °C and was stored at −70 °C until further analysis. A washout period of 7 days was selected on the basis of the terminal half-life and the effects of moxifloxacin on the QT interval [4]. To minimize variability among the three study centers, each center used the same bottled water (Volvic, Group Danone S.A., Paris, France) for drug administration and the same meal plans. To minimize variability between the ECG recording periods, the exact placement of landmarks (e.g.