675. Sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: A detailed safety review from the pivotal phase 3, global, randomized, active-controlled trial (ATTACK)

Abstract

Abstract Background SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. The primary efficacy endpoint, 28-day all-cause mortality, was achieved. The safety profile of SUL-DUR versus colistin is presented here. Methods ATTACK consisted of two parts. Part A was the randomized, non-inferiority portion in ABC hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; patients were randomized 1:1 to SUL-DUR or colistin for 7 to 14 days. Part B provided open label SUL-DUR for patients intolerant of colistin or with colistin-resistant ABC. Safety data presented here include both Part A and Part B. All patients received imipenem/cilastatin as background therapy. The primary safety objective was nephrotoxicity (RIFLE classification); other safety endpoints included treatment-emergent adverse events (TEAEs) and assessments of laboratory parameters. Results The safety population includes 203 unique patients. TEAEs were common reflecting the critical level of illness. More frequently reported with colistin treatment are severe, serious, and drug-related TEAEs (infections, renal and urinary disorders, and gastrointestinal) (Table 1). Nervous system, infections and renal disorders leading to discontinuation of study drug were more common in the colistin arm (Table 2). During treatment, liver-associated enzymes were similar between arms. Creatinine clearance measures of central tendency showed reduction during the trial in the colistin arm. Nephrotoxicity (RIFLE classification) occurred significantly less often with SUL-DUR: 13.2% (12/91) and 37.6% (32/85), difference -24.4% [p=0.0002]. Conclusion SUL-DUR treated patients had reduced nephrotoxicity, fewer drug-related TEAEs, no safety signals, and fewer TEAEs leading to discontinuation of study drug. If approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains. Disclosures Drew Lewis, MD, MTM&H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.