The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI). This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in the treatment of cUTI. Randomization will be stratified based on two criteria: (1) by primary site of infection (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72 hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of approximately 20% is planned for subjects who have received a single dose of non-study antibiotics for the acute cUTI within 72 hours prior to randomization. In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1 ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) / levofloxacin (PO).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,205
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to \<10\^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Time frame: End of Infusion
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit
This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to \<10\^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Time frame: TOC visit (14-17 days after randomization)
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Fullerton, California, United States
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Los Angeles, California, United States
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Torrance, California, United States
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Coral Gables, Florida, United States
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Doral, Florida, United States
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Miami, Florida, United States
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Columbus, Georgia, United States
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St Louis, Missouri, United States
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Las Vegas, Nevada, United States
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Baytown, Texas, United States
...and 59 more locations
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit
Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry. Clinical failure: Subjects were classified as clinical failure in the event of * Death related to cUTI at any timepoint * Persistence of clinical symptoms of cUTI or new symptoms developed * Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.
Time frame: TOC visit (14-17 days after randomization)