LAUSR

Abstract Background DLX, an anionic fluoroquinolone antibiotic with Gram-positive and Gram-negative activity, was recently approved for treatment of ABSSSI. Two global phase 3 ABSSSI trials (studies 302 and 303) included patients with cardiac or vascular disease. Methods Two multicenter, double-blind, double-dummy trials of adults with ABSSSI patients randomized 1:1 to receive either DLX monotherapy or VAN 15 mg/kg (actual body weight) with AZ for 5–14 days. Study 302 used DLX 300 mg BID IV only; study 303 used DLX 300 mg BID IV for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were objective response at 48–72 hours with ≥20% reduction in lesion size; and Investigator assessment of outcome based on resolution of signs and symptoms at Follow-up (FU day 14) and Late Follow-up (LFU day 21–28). Results In the two studies, 488 CV patients were randomized in United States, Europe, Latin America and Asia. 57% were male with mean age 59 years. Average erythema area at baseline was 446 cm2. 58% had cellulitis, 19% abscesses, 22% wound and 1% burns. Key endpoints are given in the following table. DLX, n/Total (%) VAN/AZ, n/Total (%) Objective response 48–72h (ITT) 208/260 (80.0%) 183/228 (80.3%) Investigator-Assessed Success (FU CE) 204/217 (94.0%) 176/185 (95.1%) Investigator-Assessed Success (LFU CE) 194/207 (93.7%) 173/182 (95.1%) Micro Success (FU ME) for S. aureus 72/74 (97.3%) 57/61 (93.4%) The % of CV patients with at least one treatment-related adverse event (AE) was similar for DLX (22.7%) compared with VAN/AZ (22.4%). There were 2 DLX and 5 VAN/AZ-treated CV patients discontinued due to related AEs. The most frequent treatment-related AEs were gastrointestinal including diarrhea seen in 8.2% and 3.1% of DLX and VAN/AZ patients respectively, generally mild to moderate in nature with no cases of C. difficile diarrhea. There were no cardiac events or deaths attributed to either study drug. Conclusion In CV patients, fixed dose DLX monotherapy was comparable to VAN/AZ in treatment of ABSSSI based on the early objective and investigator assessed responses at FU and LFU. DLX was also comparable to VAN/AZ in treating patients with S. aureus. There were no cardiac events or deaths in either study group. DLX appears effective and well tolerated in CV patients with ABSSSI. Disclosures G. Oguchi, Melinta Therapeutics, Inc.: Investigator, Research support. R. Beasley, Melinta Therapeutics, Inc.: Investigator, Research support. L. Lawrence, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. C. Tseng, Melinta Therapeutics, Inc.: Consultant and Research Contractor, Consulting fee. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee, Salary.