Clinical Trial: Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

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

Official Title: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ1

Brief Summary: The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

Detailed Summary: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
Sponsor: AstraZeneca

Current Primary Outcome:

• Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test [ Time Frame: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time. ]
  Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
• Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ]
  Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
• Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis
  
  

  Original Primary Outcome:

  • The proportion of patients with resolved (or return to premorbid) UTI (Urinary Track Infection) symptoms except flank pain and resolution or improvement in flank pain based on patient-reported symptom assessment response [ Time Frame: Day 5 after study drug start ]
  • The proportion of patients with a per patient microbiological eradication and resolution (or return to premorbid) of all UTI (Urinary Track Infection)-specified symptoms based on patient-reported symptom assessment response [ Time Frame: 21 to 25 day after randomization ]
  
  
  

  Current Secondary Outcome:

  • Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)
  • Per-patient Microbiological Response at LFU (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ]
    Number of patients with a favorable per patient microbiological response at LFU
  • Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)
  • Per-patient Microbiological Response at TOC (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ]
    Number of patients with a favorable per patient microbiological response at TOC
  • Per-patient Microbiological Response at LFU (ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ]
    Number of patients with a favorable per patient microbiological response at LFU
  • Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ]
    Number of patients with a favorable per-patient microbiological response at EOT (IV)
  • Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ]
    Number of patients with a favorable per patient microbiological response at TOC
  • Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ]
    Number of patients with a favorable per patient microbiological response at LFU
  • Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
  • Investigator Determined Clinical Response at TOC (mMITT Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
  • Investigator Determined Clinical Response at LFU (mMITT Analysis Set) [ Time Frame: At LFU visit. LFU visit is 45 to 52 days from Randomization. ]
    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
  • Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set) [ Time Frame: At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy ]
    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
  • Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set) [ Time Frame: At TOC visit. TOC visit is 21 to 25 days from Randomization. ]
    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical
    
    

    Original Secondary Outcome:

    • The proportion of patients with a favorable per patient microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ]
    • The proportion of patients with a favorable per patient microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ]
    • The proportion of patients with a favorable per patient microbiological response in the extended microbiological evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ]
    • The proportion of patients with resolution (or return to premorbid) of all UTI (Urinary Track Infection)-specific symptoms based on the patient-reported symptom assessment response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days and 45 to 52 days after study drug start ]
    • The proportion of favorable per-pathogen microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ]
    • The proportion of favorable per-pathogen microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The proportion of favorable per-pathogen microbiological response in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The proportion of patients with an investigator-determined clinical cure in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The proportion of patients with an investigator-determined clinical cure in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The proportion of patients with an investigator-determined clinical cure in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion,anytime between 21 - 25 days and anytime between 45 - 52 days after the start of the study drug ]
    • The proportion of patients with an investigator-determined clinical cure in the clinically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after completion of study drug, 21 to 25 days and 45 to 52 days after the start of the study drug ]
    • The proportion of patients with favorable investigator clinical response assessment in patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ]
    • The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ]
    • The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ]
    • The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ]
    • The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame:&
      
      Information By: AstraZeneca
      

      Dates:
      Date Received: May 15, 2012
      Date Started: October 2012
      Date Completion:
      Last Updated: March 8, 2016
      Last Verified: March 2016
      

    

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