A Phase 2 Study to Evaluate the Efficacy & Safety of Relebactam (REL) + Imipenem

Abstract

Background: REL (MK-7655) is a novel Class A & C ß-lactamase inhibitor intended for use with IMI for treatment of Gram-negative bacterial infections. REL restores imipenem activity against resistant Klebsiella & Pseudomonas strains. Methods: In this multicenter double-blind study, subjects ≥18 years of age with cIAI were randomized (1:1:1) to REL 250mg, REL 125mg, or placebo (pbo), each given IV with IMI every 6 hours for 4-14 days. Efficacy was evaluated at discontinuation of IV therapy (DCIV), early follow-up (EFU) & late follow-up (LFU) using test of non-inferiority (NI) with margin of 15%. The primary efficacy endpoint was the % of microbiologically evaluable (ME) subjects with favorable clinical response (CR) at DCIV. Safety analyses focused on adverse events (AEs) within 14 days of end of therapy. Results: 351 subjects were randomized, 347 were treated, and 255 (73%) were in the ME population at DCIV (55% male, mean age 49 years). The most common diagnoses were complicated appendicitis (53%) & complicated cholecystitis (17%). 27 (~10%) of ME subjects had imipenem-resistant Gram-negative infections at baseline. Efficacy & safety outcomes were similar across treatment groups. The % with favorable CR at DCIV was higher for REL 250mg (96.3%) & REL 125mg (98.8%) vs pbo (95.2%). NI was achieved. Conclusions: Both REL doses + IMI were at least as effective as IMI alone with respect to CR rate at DCIV & were generally well tolerated.