Clinical Trial: A Study of Efficacy/Safety of Intravenous S-649266 Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections

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

Official Title: A Multicenter, Double-blind, Randomized, Clinical Study to Assess the Efficacy and Safety of Intravenous S-649266 in Complicated Urinary Tract Infections With or Without Pyelonephritis or Acute Uncomp

Brief Summary: To determine the efficacy and safety of intravenous S-649266 in hospitalized adults with complicated urinary tract infections caused by Gram-negative pathogens.

Detailed Summary: The purpose of this study is to determine the efficacy and safety of intravenous S 649266 versus intravenous imipenem/cilastatin in hospitalized adults with complicated urinary tract infections with or without pyelonephritis or acute uncomplicated pyelonephritis caused by Gram-negative pathogens.
Sponsor: Shionogi

Current Primary Outcome: Composite of Clinical Cure and Microbiologic Eradication [ Time Frame: Baseline and at Test of Cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14-21) ]

Clinical and Microbiologic Response: Resolution or improvement of the symptoms of cUTI present at trial entry (and no new symptoms) and the demonstration that the bacterial pathogen found at trial entry is reduced to fewer than 10^4 CFU/mL on urine culture at the TOC (microbiological success).


Original Primary Outcome: Clinical and Microbiologic Response [ Time Frame: Baseline and at Test of Cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14-21) ]

Clinical cure in clinical outcomes (resolution of the signs and symptoms of complicated urinary tract infection [cUTI] or return to pre-infection baseline if known), and Eradication in microbiological outcomes (microbiological success) at the Test of Cure (TOC). Eradication: A urine culture shows the bacterial uropathogen(s) found at entry at ≥ 10^5 CFU/mL are reduced to < 10^4 CFU/mL


Current Secondary Outcome:

  • Microbiologic response per pathogen and per patient at early assessment (EA), EOT, TOC, and follow-up (FUP) [ Time Frame: Baseline and Early Assessment (EA; Day 4), EOT (Day 7-14), TOC (Day 14-21), and at Follow-up (FUP; 14 days after end of treatment; equivalent to Study Days 21-28) ]
    Eradication in microbiological outcomes (microbiological success), where eradication is defined as a urine culture that shows the bacterial uropathogen(s) found at entry at ≥ 10^5 CFU/mL are reduced to < 10^4 CFU/mL. A microbiological response per pathogen will be determined for each pathogen isolated at baseline. A microbiological response per patient will be determined for each patient based on individual responses.
  • Clinical response per pathogen and per patient at EA, EOT, TOC, and FUP [ Time Frame: Baseline and EA (Day 4), EOT (Day 7-14), TOC (Day 14-21), and FUP (Days 21-28) ]
    Clinical cure in clinical outcomes (resolution of the signs and symptoms of complicated urinary tract infection [cUTI] or return to pre-infection baseline if known). A clinical response per pathogen will be determined for each pathogen isolated at baseline. A clinical response per patient will be determined for each patient based on individual responses.
  • Plasma concentration of S-649266 [ Time Frame: On Day 3 of dosing; plasma sampling prior to infusion, within 15 minutes prior to end of infusion, and at 2 hours post infusion ]
    Plasma concentration of S-649266 at steady state
  • Urine concentrations of S-649266 [ Time Frame: Urine sampling 2 hours and 6 hours after end of infusion ]
    Urine concentration of S-649266 at steady state
  • Number of participants with adverse events [ Time Frame: From Baseline to the Safety Follow-up visit 28 days after end of treatment; equivalent to study Day 35 to 42 ]


Original Secondary Outcome:

  • Microbiologic response per pathogen and per patient at early assessment (EA), EOT, TOC, and follow-up (FUP) [ Time Frame: Baseline and Early Assessment (EA; Day 4), EOT (Day 7-14), TOC (Day 14-21), and at Follow-up (FUP; 14 days after end of treatment; equivalent to Study Days 21-28) ]
    Eradication in microbiological outcomes (microbiological success), where eradication is defined as a urine culture that shows the bacterial uropathogen(s) found at entry at ≥ 10^5 CFU/mL are reduced to < 10^4 CFU/mL. A microbiological response per pathogen will be determined for each pathogen isolated at baseline which may include Pseudomonas aeruginosa; Acinetobacter baumannii; Enterobacteriaceae. A microbiological response per patient will be determined for each patient based on individual responses.
  • Clinical response per pathogen and per patient at EA, EOT, TOC, and FUP [ Time Frame: Baseline and EA (Day 4), EOT (Day 7-14), TOC (Day 14-21), and FUP (Days 21-28) ]
    Clinical cure in clinical outcomes (resolution of the signs and symptoms of complicated urinary tract infection [cUTI] or return to pre-infection baseline if known). A clinical response per pathogen will be determined for each pathogen isolated at baseline, which may include Pseudomonas aeruginosa; Acinetobacter baumannii; Enterobacteriaceae. A clinical response per patient will be determined for each patient based on individual responses.
  • Plasma concentration of S-649266 [ Time Frame: On Day 3 of dosing; plasma sampling prior to infusion, within 15 minutes prior to end of infusion, and at 2 hours post infusion ]
    Plasma concentration of S-649266 at steady state
  • Urine concentrations of S-649266 [ Time Frame: Urine sampling 2 hours and 6 hours after end of infusion ]
    Urine concentration of S-649266 at steady state
  • Number of participants with adverse events [ Time Frame: From Baseline to the Safety Follow-up visit 28 days after end of treatment; equivalent to study Day 35 to 42 ]


Information By: Shionogi Inc.

Dates:
Date Received: November 11, 2014
Date Started: December 1, 2014
Date Completion:
Last Updated: April 18, 2017
Last Verified: April 2017