L-1513. Iclaprim Effect on the QT Interval: Results of Combined ASSIST Phase III Studies
Session: Poster Session: New Treatment Options in Skin and Soft Tissue Infections
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: The effect of iclaprim (ICL) on QT prolongation was assessed in two essentially identical randomized, multicenter, double-blind Phase III clinical trials.
Methods: Patients with cSSSI were randomized either to IV ICL 0.8 mg/kg q 12 hours or IV linezolid (LZD) 600 mg q 12 hours and received 10-14 days treatment. ECG monitoring was performed at Day 1 pre-dose (BL), and Day 1 and Day 4 post-dose.
Results: The ITT safety population comprised 991 patients (ICL: 500; LZD: 491). Table shows the combined QT prolongation data corrected according to Bazett’s formula (QTcB).
Table: Mean Value and Mean Change from BL in QTcB Measurements
ICLLZD
Mean value (ms)Mean change from BL (ms)Mean value (ms)Mean change from BL (ms)
Day 1 pre-doseN=499N=489
mean (SD)423.4 (23.8)--424.4 (23.6)--
Day 1 post-doseN=493N=486
mean (SD)430.5 (25.9)7.1 (13.5)425.8 (23.4)1.5 (12.7)
Day 4 post-doseN=480N=479
mean (SD)427.5 (25.6)4.0 (17.0)424.0 (23.9)-0.2 (17.6)

Mean QTcB change from BL and Day 1 and Day 4 post-dose was 7.1 and 4.0 ms respectively for ICL and 1.5 and -0.2 ms respectively for LZD.
Median QTcB intervals of >500 ms were observed in 4 patients on Day 1 (ICL: 4, LZD: 0) vs 5 patients on Day 4 (ICL: 3, LZD: 2). An increase of >60 ms from BL in QTcB interval on Day 1 was found in only one patient in each group ; on Day 4, no patients exhibited this increase.
No cardiac events were attributable to QTc prolongation in the ICL treatment arm, whereas in the LZD treatment arm one patient was withdrawn due to treatment emergent cardiovascular abnormalities. Conclusions: Intravenous ICL induced a mean change in the QTcB interval of approximately 4-6 ms compared with LZD. No cardiac events were attributable to QTc prolongation.
Anthony Leighton1, Dennis Stevens, MD, PhD, FIDSA2, Khalid Islam, PhD3, Matthew Dryden4, Paul Hadváry, PhD3, Wayne Dankner, MD, PhD5 and  P. Hadvary,
Arpida AG Role(s): Employee, Received: Salary., (1)Arpida AG, (2)VA Medical Center, Boise, ID, (3)Arpida AG, Reinach, Switzerland, (4)Royal Hampshire County Hospital, (5)PAREXEL International, Durham, NC