PO studies IV/PO studies in CAP IV/PO studies in cSSSI Antimicrobial Moxifloxacin Comparatorsb Moxifloxacin Comparatorsb Moxifloxacin Comparatorsb A B C A B C A B C A B C 787 759 384 506 596 396 516 599 165 515 187 164 486 179 Update on the Cardiac Safety of Moxifloxacin Current Drug Safety, 2012, Vol. 7, No. 2 159 Table 7. Summary of QTcB and QTcF Changes in Randomized Active-Controlled Phase II to IV Studies where ECG was Recorded at Baseline and Post-Baseline Patient Groupa Number of Patients with Valid ECG Measurement Heart Rate (Beats Per Min) (Mean ± SD) QTcB (ms) QTcB (ms) QTcF (ms) Baseline Change Baseline (Mean ± SD) (Mean ± SD) (Mean ± SD) QTcF (ms) Change (Mean ± SD) Time at which QTc Measured Baseline Post-baseline Baseline Post-baseline Baseline Day 1 Day 3 Baseline Day 1 Baseline Day 3 Baseline Day 1 Day 3 Baseline Day 1 Baseline Day 3 Baseline Day 1 Day 3 Baseline Day 1 Baseline Day 3 Baseline Day 1 Day 3 Baseline Day 1 Baseline Day 3 77.2 ± 15.4 75.4 ± 13.6 77.0 ± 16.6 74.8 ± 13.7 92.5 ± 17.6 89.6 ± 16.6 81.4 ± 15.0 93.0 ± 17.5 90.1 ± 16.7 90.5 ± 17.2 80.1 ± 14.7 91.8 ± 17.4 88.9 ± 16.7 81.0 ± 14.4 91.9 ± 17.6 89.1 ± 16.8 90.9 ± 16.7 80.8 ± 14.7 81.8 ± 15.6 81.7 ± 14.1 75.3 ± 12.3 80.6 ± 14.4 80.0 ± 14.2 82.2 ± 15.9 75.0 ± 12.4 79.6 ± 14.7 78.8 ± 13.4 73.6 ± 11.9 80.0 ± 14.3 78.3 ± 13.2 80.2 ± 14.7 73.7 ± 11.9 421.4 ± 26.9 420.8 ± 27.2 418.8 ± 30.8 419.9 ± 30.7 421.0 ± 32.5 420.0 ± 27.6 419.5 ± 28.9 421.2 ± 28.9 413.6 ± 24.7 414.0 ± 23.6 414.9 ± 26.8 412.5 ± 26.3 413.6 ± 25.8 412.2 ± 25.9 6.4 ± 25.5 0.6 ± 23.1 10.1 ± 21.9 6.6 ± 24.7 9.8 ± 21.9 5.7 ± 26.3 –1.3 ± 20.1 –3.9 ± 26.5 –1.1 ± 19.7 –3.5 ± 27.6 6.1 ± 20.2 5.0 ± 20.6 8.7 ± 16.8 4.4 ± 21.5 1.6 ± 17.0 –3.2 ± 20.2 1.8 ± 14.7 –3.6 ± 20.2 405.5 ± 27.4 405.2 ± 27.1 390.9 ± 29.8 391.7 ± 29.9 394.4 ± 31.4 392.5 ± 27.5 392.0 ± 28.5 394.2 ± 28.5 394.0 ± 23.6 395.2 ± 22.3 394.9 ± 25.9 394.5 ± 25.0 395.3 ± 24.0 393.8 ± 24.6 7.5 ± 24.8 2.0 ± 21.8 11.4 ± 21.4 14.5 ± 23.6 11.1 ± 21.0 13.3 ± 25.6 0.8 ± 18.4 4.2 ± 25.7 0.9 ± 18.2 4.3 ± 26.8 5.8 ± 17.0 9.9 ± 19.5 8.9 ± 14.6 9.9 ± 20.1 2.2 ± 14.0 1.8 ± 17.6 3.1 ± 12.3 1.8 ± 17.3 ECG = electrocardiographic; SD = standard deviation; PO = oral administration; IV/PO = sequential intravenous/oral administration; CAP = community-acquired pneumonia, cSSSI = complicated skin and skin structure infection; = not applicable. aGroup A = patients with ECG measurements at baseline, Day 1 and Day 3; Group B = patients with ECG measurements at baseline and Day 1; Group C = patients with ECG measurements at baseline and Day 3. bFor a list of comparators see Table 1. IV/PO indications. At each measurement point (baseline, Day 1, Day 3 [IV/PO] or post-baseline [PO] of antimicrobial treatment), there was wide between-patient variation in QTc intervals, as demonstrated by the large and overlapping SDs and ranges. The change in QTc from baseline was as expected for moxifloxacin [11, 19, 25, 36-39], with QTcB values up to 10 ms on Day 1 following the initial intravenous treatment and falling to 4–7 ms by Day 3 when steady state could be expected. The latter increase is similar to the post- baseline levels observed in the PO population. The increase in QTcB with moxifloxacin was higher after IV/PO than PO administration. This is likely to be explained by the fact that patients receiving initially IV moxifloxacin were more severely ill and had a higher baseline heart rate than those receiving PO moxifloxacin.