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

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

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).

Study Overview

• Status: Completed
• Conditions: cUTI
• Intervention / Treatment: Drug: Levofloxacin; Drug: Eravacycline

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.

• Study Type: Interventional
• Enrollment (Actual): 908
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Gabrovo, Bulgaria
    • Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Nephrology
  • Montana, Bulgaria
    • Multiprofile Hospital for Active Treatment "Dr. Stamen Iliev", Montana, Department of Nephrology and Dialysis
  • Pleven, Bulgaria
    • University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic
  • Rousse, Bulgaria
    • Multiprofile Hospital for Active Treatment, Ruse, Department of Urology
  • Sofia, Bulgaria
    • Multiprofile Hospital for Active Treatment, Sofia at Military Medical Academy, General Urology Clinic
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment "Aleksandrovska", Sofia, Department of Laparoscopic Urology
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic
  • Veliko Tarnovo, Bulgaria
    • Multiprofile Regional Hospital for Active Treatment "Dr. Stefan Cherkezov", Veliko Tarnovo, Department of Urology
• Colombia
  • Armenia, Colombia
    • Fundacion Cardiomet
  • Barranquilla, Colombia
    • De la Costa Clinic. Ltd. Research Centre
• Czechia
  • Brno, Czechia
    • University Hospital Brno, Clinic of Urology
  • Hradec Kralove, Czechia
    • University Hospital Hradec Kralove, Clinic of Urology
  • Novy Jicin, Czechia
    • Hospital Novy Jicin, Department of Urology
  • Olomouc, Czechia
    • University Hospital Olomouc
  • Prague, Czechia
    • Thomayer Hospital, Department of Urology
• Estonia
  • Kohtla-Jarve, Estonia
    • East Viru Central Hospital, Surgery Clinic
  • Tallinn, Estonia
    • East Tallinn Central Hospital, Department of Internal Medicine
  • Tallinn, Estonia
    • West Tallinn Central Hospital, Department of Urology
  • Tartu, Estonia
    • Tartu University Hospital, Surgery Clinic, Department of Urology and Renal Transplantation
• Georgia
  • Kutaisi, Georgia
    • Western Georgia National Medical Center
  • Tbilisi, Georgia
    • Aversi Clinic
  • Tbilisi, Georgia
    • Research Institute of Clinical Medicine
  • Tbilisi, Georgia
    • Modern Medical Technologies - Guram Karazanashvili's clinic
  • Tbilisi, Georgia
    • Tsulukidze National Center of Urology
• Greece
  • Kolonaki, Greece
    • Evaggelismos Hospital
  • Thessaloníki, Greece
    • Papageorgiou General Hospital
• Hungary
  • Baja, Hungary
    • Principal SMO Kft.
  • Budapest, Hungary
    • Jahn Ferenc South Pest Hospital, Department of Urology
  • Gyor, Hungary
    • Petz Aladar County Teaching Hospital, Department of Urology
  • Sopron, Hungary
    • Elisabeth Teaching Hospital and Rehabilitation Institute of Sopron, Department of Urology
  • Szentes, Hungary
    • Csongrad County Dr. Bugyi Istvan Hospital, Department of Urology
  • Tatabanya, Hungary
    • St. Borbala Hospital, Department of Urology
• Israel
  • Haifa, Israel
    • Zion Medical Center
• Italy
  • Castellanza, Italy
    • Hospital Mater Domini
• Latvia
  • Liepaja, Latvia
    • Liepajas Regional Hospital
  • Riga, Latvia
    • P. Stradins Clinical University Hospital
  • Riga, Latvia
    • Riga East University Hospital, LLC
  • Riga, Latvia
    • SIA 'URO' Clinic
  • Valmiera, Latvia
    • Vidzemes Hospital
• Mexico
  • Guadalajara, Mexico
    • Hospital Civil Fray Antonio Alcalde
  • Guadalajara, Mexico
    • Hospital Civil Guadalajara Dr. Juan I. Mendoza
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • National Scientific Practical Center for Emergency Medicine, Department of Urology
  • Chisinau, Moldova, Republic of
    • Republican Clinical Hospital, Department of Urology
• Poland
  • Katowice, Poland
    • Boni Fratres Catoviensis Sp. z o.o., Department of Internal Diseases with Cardiologic Diagnostics Unit
  • Lodz, Poland
    • Military Medical Academy University Teaching Hospital - Central Veterans' Hospital, Clinical and Didactic Center of the Medical University of Lodz, Teaching Department of Nephrology, Hypertension and Renal Transplantation
  • Oswiecim, Poland
    • Medicome Sp. z o.o.
  • Piaseczno, Poland
    • HEUREKA Hanna Szalecka
  • Zamość, Poland
    • Pope John Paul 2nd Independent Public Provincial Hospital
• Romania
  • Brasov, Romania
    • Emergency Clinical County Hospital Brasov
  • Bucharest, Romania
    • "Prof. Dr. Th. Burghele" Clinical Hospital
  • Bucharest, Romania
    • Delta Hospital
  • Craiova, Romania
    • Craiova Emergency Clinical County Hospital
  • Iași, Romania
    • Clinical Hospital "Dr. C. I. Parhon"
  • Oradea, Romania
    • Oradea Clinical Municipal Hospital "Dr. Gavril Curteanu"
  • Sibiu, Romania
    • Sibiu County Emergency Clinical Hospital
• Russian Federation
  • Moscow, Russian Federation
    • Central Clinical Hospital of Civil Aviation
  • Moscow, Russian Federation
    • City Clinical Hospital #57 under Moscow Healthcare Department
  • Moscow, Russian Federation
    • Federal Clinical Center for High Medical Technologies
  • Novosibirsk, Russian Federation
    • City Clinical Hospital of Emergency Care #2
  • Penza, Russian Federation
    • Penza Regional Clinical Hospital n.a. N.N. Burdenko
  • Rostov-on-Don, Russian Federation
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation
    • North-Western State Medical University n.a. I.I. Mechnikov
  • Saint Petersburg, Russian Federation
    • Saint-Petersburg Scientific Research Institute for Phthisiopulmonology
  • Saint Petersburg, Russian Federation
    • St. Petersburg Clinical Hospital under the Russian Academy of Sciences
  • Saint Petersburg, Russian Federation
    • St. Petersburg State Healthcare Institution: City Hospital #15
  • Saint Petersburg, Russian Federation
    • St. Petersburg State Healthcare Institution: St. George the Martyr City Hospital
  • Saint Petersburg, Russian Federation
    • St. Petersburg State-Funded Healthcare Institution: City Hospital #26
  • Saratov, Russian Federation
    • Saratov State Medical University n.a. V.I. Razumovsky
  • Smolensk, Russian Federation
    • Smolensk Regional Clinical Hospital
  • Veliky Novgorod, Russian Federation
    • Novgorod Regional Clinical Hospital
  • Vsevolozhsk, Russian Federation
    • Vsevolozhsk Clinical Central District Hospital
• South Africa
  • Benoni, South Africa
    • Lakeview Hospital
  • Kempton Park, South Africa
    • Clinresco Centres
  • Middleburg, South Africa
    • Mzansi Ethical Research Centre
  • Port Elizabeth, South Africa
    • St. Georges Hospital
• Ukraine
  • Chernivtsi, Ukraine
    • Regional Municipal Institution "Chernivtsi Regional Hospital"
  • Dnipropetrovsk, Ukraine
    • Dnipropetrovsk City Multispecialty Clinical Hospital #4
  • Dnipropetrovsk, Ukraine
    • Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital
  • Ivano-Frankivs'k, Ukraine
    • Ivano-Frankivsk Regional Clinical Hospital
  • Ivano-Frankivs'k, Ukraine
    • Ivano-Frankivsk City Clinical Hospital #1
  • Kharkiv, Ukraine
    • O.I. Meschaninov Clinical Hospital of Emergency and Urgent Medical Care
  • Kharkiv, Ukraine
    • Shapoval Regional Clinical Center of Urology and Nephrology
  • Khmel'nyts'kyy, Ukraine
    • Khmelnytskyi Regional Hospital
  • Kyiv, Ukraine
    • Institute of Urology
  • L'viv, Ukraine
    • Lviv Regional Clinical Hospital
  • Luts'k, Ukraine
    • Volyn Regional Clinical Hospital
  • Mykolaiv, Ukraine
    • Mykolaiv Regional Hospital, Center for Nephrology and Dialysis
  • Odesa, Ukraine
    • City Clinical Hospital #10, Urology Department #1
  • Odessa, Ukraine
    • Odesa Regional Clinical Hospital
  • Poltava, Ukraine
    • Poltava M.V. Sklifosovskyi Regional Clinical Hospital
  • Uzhhorod, Ukraine
    • State Institution: Uzhhorod Railway Station Clinical Hospital under State Territorial Industry-Specific Association:Lviv Railway
  • Vinnytsya, Ukraine
    • Vinnytsia M.I. Pyrohov Regional Clinical Hospital
  • Zaporizhzhya, Ukraine
    • Municipal Institution "Zaporizhzhia Reqional Clinical Hospital" of Zaporizhzhia Regional Councill
• United States
  • California
    • San Diego, California, United States
      • San Diego Clinical Trials
    • Torrance, California, United States
      • Harbor-UCLA Medical Center
  • Florida
    • Tampa, Florida, United States
      • Tampa General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Centre
  • Ohio
    • Columbus, Ohio, United States
      • Columbus Regional Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Levaquin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants In The Microbiological Intent-To-Treat (Micro-ITT) Population With A Responder Outcome At The Post-Treatment (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.	PT Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response	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.	PT Visit
Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response	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.	PT Visit

Collaborators and Investigators

• Sponsor: Tetraphase Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2014
• Primary Completion (ACTUAL): June 3, 2015
• Study Completion (ACTUAL): August 21, 2015

Study Registration Dates

• First Submitted: October 28, 2013
• First Submitted That Met QC Criteria: November 1, 2013
• First Posted (ESTIMATE): November 8, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin
• Other Study ID Numbers: TP-434-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No