152 Current Drug Safety, 2012, Vol. 7, No. 2 RESULTS Demographics A total of 29,548 patients were enrolled in 64 trials (49 PO, 15 IV/PO) of moxifloxacin versus comparator antimicrobials. Of these, 28,144 patients were included in the pooled safety population; 21,298 had received PO antimicrobials (10,613 moxifloxacin, 10,685 comparators) and 6846 had received sequential IV/PO antimicrobials (3431 moxifloxacin, 3415 comparators). Within the PO group or the IV/PO group there were no relevant differences in patient characteristics between moxifloxacin and comparator groups (Table 2). However, there were differences in characteristics between patients given PO or IV/PO antimicrobials. In the PO group, most patients had received outpatient antimicrobial treatment for the respiratory indications of ABS, AECB, and CAP, while in the IV/PO group, most patients were hospitalized with either CAP or cSSSI. Patients in the PO group were about 8 years younger than those in the IV/PO group, with 22% in the PO group and 40% in the IV/PO group being 65 years of age. There were also more women in the PO group than the IV/PO group (54% vs 39%, respectively). Finally, in both treatment arms patients in the IV/PO group compared with those in the PO group were more likely to be taking comedications known to cause QT prolongation (IV/PO: MXF: 10.0%, COMP: 8.7% vs PO: MXF: 4.1%, COMP: 4.0%, respectively) and to have cardiac disease (IV/PO: Haverkamp et al. MXF: 34.0%, COMP: 33.3% vs PO: MXF: 13.9%, COMP: 13.1%, respectively). There were some differences in heart rates at baseline (Tables 2 and 7). IV/PO CAP patients presented with the highest mean baseline heart rate values (moxifloxacin 90.5 beats per minutes [bpm], comparators 90.9 bpm), followed by those with IV/PO cSSSI patients (moxifloxacin 82.2 bpm, comparators 80.2 bpm). Patients receiving PO therapy had the lowest heart rates (moxifloxacin 77.2 bpm, comparators 77.0 bpm). AEs and Treatment-Emergent Overall Incidence of Cardiac AEs Treatment-Emergent Serious AEs There was no evidence of any excess of cardiac AEs with moxifloxacin versus comparators in the PO or IV/PO populations (Table 3). In the overall safety population, the number of patients with treatment-emergent cardiac AEs was low for both treatment arms irrespective of route of treatment administration. Of patients receiving PO therapy, 698/10,613 (6.6%) in the moxifloxacin arm and 619/10,685 (5.8%) in the comparator arm experienced a treatment- emergent cardiac AE. In those receiving IV/PO therapy, equivalent numbers were 377/3431 (11.0%) for moxifloxacin and 410/3415 (12.0%) for comparators. Treatment-emergent serious cardiac AEs also occurred in low numbers both in the PO (moxifloxacin: 75/10,613 [0.7%]; comparators 72/10,685 [0.7%]) and IV/PO groups Table 2. Baseline Patient Characteristics Across All Phase II to IV Randomized Active-Controlled Studies with PO or IV/PO Moxifloxacin PO = oral administration; IV/PO = sequential intravenous/oral administration; SD = standard deviation; = not applicable. aFor a list of comparators see Table 1. bPO: n = 7499 moxifloxacin, n = 7170 comparators; IV/PO: n = 3401 moxifloxacin, n = 3398 comparators. cComedications known to cause QTc prolongation were selected according to [30] and [31]. dUncomplicated skin and skin structure infection, complicated urinary tract infection, streptococcal pharyngitis. eAspiration pneumonia or lung abscess, hospital-acquired pneumonia. PO (N = 21,298) IV/PO (N = 6846) Comparatorsa (N = 10,685) Moxifloxacin (N = 3431) Comparatorsa (N = 3415) 48.0 ± 17.9 2403 (22.5) 5817 (54.4) 25.9 ± 5.8 83.0 ± 13.7 1402 (13.1) 426 (4.0) 2641 (24.7) 3820 (35.8) 1822 (17.1) 919 (8.6) 1483d (13.9) 56.8 ± 19.1 1373 (40.0) 1349 (39.3) 26.9 ± 6.6 93.7 ± 18.2 1167 (34.0) 343 (10.0) 1511 (44.0) 1130 (32.9) 618 (18.0) 172e (5.0) 56.1 ± 19.2 1334 (39.1) 1323 (38.7) 26.7 ± 6.4 93.7 ± 18.1 1136 (33.3) 298 (8.7) 1539 (45.1) 1077 (31.5) 622 (18.2) 177e (5.2) Age, mean ± SD (years) Age 65 years, n (%) Female sex, n (%) Body mass index, mean ± SD (kg/m2) Heart rate, mean ± SD (bpm)b Cardiac disease, n (%) Comedication known to cause QT prolongation, n (%)c Indication, n (%) Acute bacterial sinusitis Acute exacerbation of chronic bronchitis Community-acquired pneumonia Complicated skin and skin structure infection Complicated intra-abdominal infection Uncomplicated pelvic inflammatory disease Other Moxifloxacin (N = 10,613) 48.2 ± 18.0 2451 (23.1) 5773 (54.4) 26.0 ± 5.9 82.8 ± 13.6 1475 (13.9) 430 (4.1) 2331 (22.0) 4029 (38.0) 1790 (16.9) 946 (8.9) 1517d (14.3)