An Open-label, Randomized, Single Period, Parallel-Cohort Study To Evaluate Serum and Pulmonary Pharmacokinetics Following Single and Multiple Dose Administration of Intravenous GSK2251052 in Healthy Adult Subjects

GSK2251052 is a member of a novel mechanistic and structural class of antibiotics that inhibits the bacterial enzyme leucyl tRNA synthetase (LeuRS) by forming a boron adduct with tRNA and is currently in development for the treatment of hospital acquired Gram-negative infections (including E. coli, K. pneumoniae, and Enterobacter spp.). This is an open-label, randomized, single period, parallel-cohort pharmacokinetic study to evaluate serum and pulmonary pharmacokinetics following single dose and multiple dose administration of intravenous GSK2251052. In Cohort 1, approximately 15 healthy adult subjects will be randomized to receive a single IV dose of GSK2251052 1500 mg in the fasted state. Following the dose, bronchoalveolar lavage (BAL) fluid and serial plasma samples will be collected for determination of GSK2251052 parent and metabolite concentrations. In Cohort 2, approximately 15 healthy adult subjects will receive GSK2251052 1500 mg IV BID x 5 doses (Cohort 2). Following the last dose in the fasted state, bronchoalveolar lavage (BAL) fluid and serial plasma samples will be collected for determination of GSK2251052 parent and metabolite concentrations. Vital signs, ECGs, and adverse events will be monitored throughout the study. A follow up visit will occur 10 to 14 days after the last dose of study drug.