Clinical Trial: Efficacy, Safety, Tolerability of Carbavance Compared to Piperacillin/Tazobactam in Complicated Urinary Tract Infections (cUTIs), Including Acute Pyelonephritis (AP), in Adults

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

Official Title: A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy Study to Evaluate the Efficacy, Safety, and Tolerability of Carbavance (Meropenem/Vaborbactam) Compared to Piperacillin/Tazobactam in th

Brief Summary: Carbavance, (meropenem/vaborbactam) is being compared to piperacillin/tazobactam in the treatment of adults with cUTIs or AP

Detailed Summary:

In the current era of increased resistance to extended spectrum cephalosporins, carbapenem antimicrobial agents are frequently the antibiotics of "last defense" for the most resistant pathogens in serious infections, including those found in cUTIs. The recent dissemination of serine carbapenemases in Enterobacteriaceae in many hospitals worldwide now poses a considerable threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

Rempex is developing Carbavance (meropenem/vaborbactam) administered as a fixed combination by intravenous (IV) infusion, to treat serious Gram-negative infections, such as cUTIs, including those infections caused by bacteria resistant to currently available carbapenems.


Sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

Current Primary Outcome: Efficacy measured at the End of IV Treatment visit (FDA), or at the Test Of Cure visit (EMA). [ Time Frame: EOIVT at day 5 - 14 (FDA), TOC at day 15-23 (EMA) ]

For the FDA: the proportion of subjects in the microbiologic Modified Intent To Treat Population (m-MITT) who achieve overall success at the EOIVT visit. Overall success is achieved with a clinical outcome of Cure or Improvement and microbiologic outcome of Eradication at EOIVT. Cure is defined as the complete resolution or significant improvement of the baseline signs and symptoms. Improvement is defined as lessening, incomplete resolution, or no worsening of the baseline signs and symptoms. Eradication is defined as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <104 CFU/mL of urine.

For the European Medicines Agency (EMA): the proportion of subjects in the co-primary m-MITT and Microbiologic Evaluable (ME) Populations who achieve a microbiologic outcome of Eradication at the TOC visit. Eradication is defined as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <103 CFU/mL of urine.



Original Primary Outcome: Efficacy measured at the End of IV Treatment visit (FDA), or at the Test Of Cure visit (EMA). [ Time Frame: EOIVT at day 5 - 14 (FDA), TOC at day 17-21 (EMA) ]

For the FDA: the proportion of subjects in the microbiologic Modified Intent To Treat Population (m-MITT) who achieve overall success at the EOIVT visit. Overall success is achieved with a clinical outcome of Cure or Improvement and microbiologic outcome of Eradication at EOIVT. Cure is defined as the complete resolution or significant improvement of the baseline signs and symptoms. Improvement is defined as lessening, incomplete resolution, or no worsening of the baseline signs and symptoms. Eradication is defined as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <104 CFU/mL of urine.

For the European Medicines Agency (EMA): the proportion of subjects in the co-primary m-MITT and Microbiologic Evaluable (ME) Populations who achieve a microbiologic outcome of Eradication at the TOC visit. Eradication is defined as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <103 CFU/mL of urine.



Current Secondary Outcome:

  • Proportion of subjects in m-MITT Population with overall success at the End of IV Treatment visit or at the Test Of Cure visit [ Time Frame: at both EOIVT (day 5 - 14) & TOC (day 15 - 23) ]
  • Proportion of subjects in m-MITT & ME Populations with microbiologic outcome of Eradication to <10^4 CFU/mL of urine (FDA) / <10^3 CFU/mL of urine (EMA) [ Time Frame: at Day 3, EOIVT (day 5 - 14), EOT (day 10-14), TOC (day 15 - 23), and LFU (day 22 - 30) ]
  • Proportion of subjects with a clinical outcome of Cure in the m-MITT, CE, and ME Populations [ Time Frame: at Day 3, EOIVT (day 5 - 14), EOT (day 10-14), TOC (day 15 - 23), and LFU (day 22 - 30) ]
  • Per-pathogen outcome in the m-MITT and ME Populations [ Time Frame: at Day 3, EOIVT (day 5 - 14), EOT (day 10-14), TOC (day 15 - 23), and LFU (day 22 - 30) ]
  • Pharmacokinetic characterization of plasma exposure of meropenem and vaborbactam [ Time Frame: Day 1 to EOIVT (day 5 - 14) ]
  • Safety and tolerability profile of Carbavance by incidence and severity of AEs & SAEs, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and physical examinations [ Time Frame: Screening to LFU (day 22 - 30) ]
    Composite endpoint in the Safety Population


Original Secondary Outcome:

Information By: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

Dates:
Date Received: June 16, 2014
Date Started: November 2014
Date Completion:
Last Updated: December 1, 2016
Last Verified: November 2016