Phase 3 study comparing tigecycline (tgc) and ertapenem (ert) in patients (pts) with diabetic foot infections (dfi) with and without osteomyelitis

BACKGROUND: TGC is a glycylcycline-class antibacterial with a broad spectrum of in vitro activity including gram-positive, -negative, and anaerobic organisms, indicated for the treatment of complicated skin and skin structure infections (cSSSI). Based on its in vitro activity and its effectiveness in pts with cSSSI, including a subpopulation of pts with diabetes evaluated in two large-scale phase 3 cSSSI trials, a dedicated study to evaluate TGC in the treatment of DFI was performed. METHODS: Phase 3, randomized, double-blind study, conducted in pts with DFI, with or without osteomyelitis, to determine the efficacy and safety of 150 mg IV once-daily TGC vs. 1 g once-daily ERT, ± adjunctive IV vancomycin placebo (TGC arm) or vancomycin (ERT arm). RESULTS: Among 944 DFI pts without osteomyelitis who received ≥1 dose of study drug, >85% had diabetes type 2, ~90% had PEDIS infection grade 2/3 and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.5% of TGC- and 82.5% of ERT-treated pts were clinically cured. Corresponding rates for the clinical modified intent-to-treat population were 71.4% and 77.9%, respectively. Clinical cure rates were low (<36%) for a subset of TGC-treated patients with osteomyelitis. Nausea and vomiting occurred significantly more often after TGC, which led to discontinuation significantly more often compared with ERT-treated patients. CONCLUSION: Although TGC has been shown to be efficacious in pts with cSSSI, the 150 mg once-daily regimen evaluated in this trial did not meet non-inferiority criteria compared with ERT in the primary study in pts with DFI. For the substudy in pts with osteomyelitis, cure rates for TGC were low. Higher rates of nausea and vomiting were observed for TGC in this trial than in other phase 3 studies, with higher discontinuation rates for these adverse events. The safety profile of TGC was otherwise similar to what has already been established.