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Efficacy and Safety Study of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections

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ClinicalTrials.gov Identifier: NCT01978938
Recruitment Status : Completed
First Posted : November 8, 2013
Results First Posted : December 11, 2018
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Tetraphase Pharmaceuticals, Inc.

Brief Summary:
This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy and safety of eravacycline compared with levofloxacin in participants with complicated urinary tract infections (cUTI).

Condition or disease Intervention/treatment Phase
cUTI Drug: Eravacycline Drug: Levofloxacin Phase 3

Detailed Description:
This study began with a 3-arm Lead-in portion to determine the oral (PO) dosing (200 or 250 milligrams [mg]) of eravacycline to be used with intravenously (IV) administered eravacycline for the Pivotal portion (2 arms). A PO dose of 200 mg was selected based on the unblinded Lead-in analysis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 908 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Except for the responsible study site pharmacist or designee and separate unblinded clinical research associates to monitor drug supply and adherence to study drug blinding and randomization procedures, all study staff and participants were blinded to treatment assignment.
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Double-dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections
Actual Study Start Date : October 6, 2014
Actual Primary Completion Date : June 3, 2015
Actual Study Completion Date : August 21, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Eravacycline
Eravacycline was administered IV at a dose of 1.5 mg per kilogram (kg) of body weight every 24 hours (q24h). At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO twice a day for a total therapy of 7 dosing cycles.
Drug: Eravacycline
Other Name: TP-434

Active Comparator: Levofloxacin
Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO once a day for a total therapy of 7 dosing cycles.
Drug: Levofloxacin
Other Name: Levaquin




Primary Outcome Measures :
  1. Participants In The Microbiological Intent-To-Treat (Micro-ITT) Population With A Responder Outcome At The Post-Treatment (PT) Visit [ Time Frame: PT Visit ]
    This was the primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to levofloxacin 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.


Secondary Outcome Measures :
  1. Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response [ Time Frame: PT Visit ]
    This outcome measure (FDA and the European Medicines Agency [EMA]) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the micro-MITT population. Responses were success, failure, or indeterminate/missing. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond end of therapy (EOT) to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available.

  2. Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response [ Time Frame: PT Visit ]
    This outcome measure (FDA and EMA) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the ME population. Responses were either success or failure. Indeterminate/missing responses were not included. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond EOT to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available. Populations: ME, all micro-ITT and clinically-evaluable (CE) participants with a suitable urine specimen and an interpretable urine culture; micro-ITT, all participants with ≥1 baseline bacterial pathogen from a urine or blood culture that caused a UTI against which eravacycline had expected antibacterial activity; ITT, all randomized participants, regardless of receiving study drug or not.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Male and female participants with either:

a. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), OR b. cUTI with at least 1 of the following conditions associated with a risk for developing cUTI: i. Indwelling urinary catheter ii. Urinary retention (approximately 100 milliliters of residual urine after voiding) iii. Neurogenic bladder iv. Partial obstructive uropathy (such as, nephrolithiasis, bladder stones, and ureteral strictures) v. Azotemia of renal origin (not congestive heart failure or volume related) such that the serum blood urea nitrogen (BUN) is elevated (>20 mg/deciliters) AND the serum BUN: creatinine ratio is <15 vi. Surgically modified or abnormal urinary tract anatomy (such as, bladder diverticula, redundant urine collection system) EXCEPT surgery within the last month

Exclusion Criteria:

1. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in participants with cUTI, including:

  1. Participants with a history of a levofloxacin-resistant urinary tract infection
  2. Likely to receive ongoing antibacterial drug prophylaxis prior to the late Post-Treatment visit (such as, participants with vesiculo-ureteral reflux)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01978938


Locations
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Sponsors and Collaborators
Tetraphase Pharmaceuticals, Inc.
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Responsible Party: Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01978938    
Other Study ID Numbers: TP-434-010
First Posted: November 8, 2013    Key Record Dates
Results First Posted: December 11, 2018
Last Update Posted: April 10, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Urinary Tract Infections
Infection
Urologic Diseases
Levofloxacin
Ofloxacin
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors