Abstract
BACKGROUND: The worldwide spread of serine carbapenemases threatens carbapenems. VABOMERE (combination of meropenem and vaborbactam (MV), is a new class of beta-lactamase inhibitors including inhibition of Klebsiella pneumoniae. The PK, safety, and efficacy data of MV in adults support study in pediatrics. METHODS: Phase 1, open-label, dose-finding study. Pediatric subjects, 3 mos. to < 18 yrs already on antibiotics received a single-dose weight based infusion of MV over 3 hr. Blood samples were drawn pre-dose, 3,4, and 6 hr. for PK parameters. Population PK model included weight as a covariate. Safety assessments included AEs, vital signs, safety labs, physical exams, infusion tolerance, ECG. A DSMB reviewed safety and PK data before enrolling next cohort. RESULTS: MV was well-tolerated and safe in all age groups. Clearance per kg body weight of both M and V increased with decreasing body weight over all age groups suggesting an allometric relationship. [Table: see text] [Table: see text] CONCLUSION: Targeted AUC(0-8) efficacious in adult trials ranges of 91.7-513 mg•hr/L (meropenem) and 131-494 mg•hr/L (vaborbactam) were achieved in all pediatric cohorts. DISCLOSURES: Paula M. Bokesch, MD, Melinta Therapeutics: Advisor/Consultant Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Randall K. Hoover, Ph.D., Melinta Therapeutics: Advisor/Consultant Sandra McCurdy, MS, Melinta Therapeutics: Employee