Clinical Trial: GSK2251052 in Complicated Urinary Tract Infection

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Randomised, Double-blind, Dose-finding, Multicenter Study of the Safety, Tolerability, and Efficacy of GSK2251052 Therapy Compared to Imipenem-cilastatin in the Treatment of Adult Subjects With Febr

Brief Summary: This study is being conducted to evaluate the safety, efficacy (clinical and microbiological), pharmacokinetics/pharmacodynamics of GSK2251052 and to assess whether it would be a suitable antibiotic for the treatment for febrile lower cUTI and pyelonephritis(complicated and uncomplicated). GSK2251052 will be compared to imipenem-cilastatin, which is an antibiotic commonly used to treat serious cUTI infections. GSK2251052 has a spectrum of microbiological activity that includes pathogens responsible for cUTI.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

• Safety outcome On Therapy [ Time Frame: On therapy (days 1-14) ]
  Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
• Safety outcome at End of Therapy [ Time Frame: End of therapy (0-24 hours post-therapy) ]
  Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
• Safety outcome at Test of Cure [ Time Frame: Test of cure (5-9 days post-therapy) ]
  Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least 3 days of study medication
• Safety outcome at Early Follow-up [ Time Frame: Early Follow-up (14-17 days post-therapy) ]
  Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at 3 days of study medication
• Safety outcome at Follow-up [ Time Frame: Follow-up (21-28 days post-therapy) ]
  Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
• Efficacy Outcome - Therapeutic Response [ Time Fra
  
  

  Original Primary Outcome:

  • Safety outcome On Therapy [ Time Frame: On therapy (days 1-14) ]
    Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
  • Safety outcome at End of Therapy [ Time Frame: End of therapy (0-24 hours post-therapy) ]
    Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
  • Safety outcome at Test of Cure [ Time Frame: Test of cure (5-9 days post-therapy) ]
    Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
  • Safety outcome at Early Follow-up [ Time Frame: Early Follow-up (14-17 days post-therapy) ]
    Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
  • Safety outcome at Follow-up [ Time Frame: Follow-up (21-28 days post-therapy) ]
    Evaluation of data from clinical laboratory tests, spontaneous/elicited adverse event reporting, ECGs and vital signs in all enrolled subjects who had at least one dose of study medication
  • Efficacy Outcome - Therapeutic Response [ Tim
    
    

    Current Secondary Outcome:

    • Microbiological response [ Time Frame: End of IV therapy (0-24 hours post-therapy) ]
      Microbiological success or failure in subjects who have a qualifying Gram-negative uropathogen at Baseline and who have a minimum of 5 days of IV therapy
    • Clinical Response [ Time Frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy) ]
      Clinical success or failure in subjects who have a qualifying Gram-negative uropathogen at Baseline and who have a minimum of 5 days of IV therapy
    • Therapeutic response [ Time Frame: End of IV therapy (0-24 hours post-therpay; Late Follow-up (21-28 days post-therapy) ]
      Combined per-subject clinical and microbiological response in subjects who have a qualifying Gram-negative uropathogen at Baseline and have had a minimum of 5 days of IV therapy
    • Maximum plasma concentration (Cmax) of GSK2251052 [ Time Frame: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      Pharmcokinetics (PK) in all subjects
    • Area under the concentration time curve (AUC) of GSK2251052 [ Time Frame: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      PK in all subjects
    • Time to Cmax (Tmax) of GSK2251052 [ Time Frame: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      PK in all subjects
    • Cmax of GSK2251052 using Non-intensive PK sampling [ Time Frame: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      Non-intensive PK sampling for all patients who are not participating in Intensive PK Sampling
    • AUC of GSK2251052 using Non-intensive PK sampling [ Time Frame: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      Non-intensive PK sampling for all patients who are not participating in Intensive PK Sampling
    • Tmax of GSK2251052 using Non-intensive PK sampling [ Time Frame: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose ]
      Non-intensive PK sampling for all patients who are not participating in Intensive PK Sampling
    • Cmax of GSK2251052 using intensive PK sampling [ Time Frame: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose ]
      Sub-set of approximately 15 patients
    • AUC of GSK2251052 using intensive PK sampling [ Time Frame: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose ]
      Sub-set of approximately 15 patients
    • Tmax of GSK2251052 using intensive PK sampling [ Time Frame: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose ]
      Sub-set of approximately 15 patients
    
    
    

    Original Secondary Outcome: Same as current
    
    Information By: GlaxoSmithKline
    

    Dates:
    Date Received: June 9, 2011
    Date Started: June 2011
    Date Completion:
    Last Updated: July 24, 2014
    Last Verified: February 2014