Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief Summary:

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.


Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Epithelial lining fluid (ELF)/ plasma ratios for GSK2251052 at early, mid, and late dosing interval timepoints following intravenous administration of 1500 mg q12h. [ Time Frame: up to 3 days ]
  • Alveolar macrophage (AM)/ plasma ratios for GSK2251052 at early, mid, and late dosing interval timepoints following intravenous administration of 1500 mg q12h. [ Time Frame: up to 3 days ]


Original Primary Outcome:

  • Epithelial lining fluid (ELF)/ plasma ratios for GSK2251052 at early, mid, and late dosing interval timepoints following intravenous administration of 1500 mg q12h. [ Time Frame: 1 to 3 days ]
  • Alveolar macrophage (AM)/ plasma ratios for GSK2251052 at early, mid, and late dosing interval timepoints following intravenous administration of 1500 mg q12h. [ Time Frame: 1 to 3 days ]


Current Secondary Outcome:

  • Plasma AUC (0-t), Cmax, CL, Vss, and t½, following intravenous administration of GSK2251052, as permitted by the data. [ Time Frame: up to 3 days ]
  • GSK2251052 concentrations in urine following single and repeat dose administration [ Time Frame: up to 3 days ]
  • Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, cardiac monitoring, and vital signs assessments. [ Time Frame: up to 14 days ]


Original Secondary Outcome:

  • Plasma AUC (0-t), Cmax, CL, Vss, and t½, following intravenous administration of GSK2251052, as permitted by the data. [ Time Frame: 1 to 3 days ]
  • GSK2251052 concentrations in urine following single and repeat dose administration [ Time Frame: 1 to 3 days ]
  • Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, cardiac monitoring, and vital signs assessments. [ Time Frame: 14 days ]


Information By: GlaxoSmithKline

Dates:
Date Received: December 16, 2010
Date Started: January 2011
Date Completion:
Last Updated: March 1, 2012
Last Verified: February 2012