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

NCT01978938 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: TP-434-010
• Study Type: interventional
• Target: 908
• Locations: 18 countries
• Sites: 99

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).

Conditions

cUTI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response

  PT Visit

• Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response

  PT Visit

Study Arms (2)

Eravacycline

EXPERIMENTAL

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

Levofloxacin

ACTIVE COMPARATOR

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

Interventions

Eravacycline DRUG

Also known as: TP-434

Eravacycline

Levofloxacin DRUG

Also known as: Levaquin

Levofloxacin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in participants with cUTI, including:
• Participants with a history of a levofloxacin-resistant urinary tract infection
• Likely to receive ongoing antibacterial drug prophylaxis prior to the late Post-Treatment visit (such as, participants with vesiculo-ureteral reflux)

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead

Study Sites (99)

San Diego Clinical Trials

San Diego, California, United States

Location

Harbor-UCLA Medical Center

Torrance, California, United States

Location

Tampa General Hospital

Tampa, Florida, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Sunrise Hospital and Medical Centre

Las Vegas, Nevada, 89109, United States

Location

Columbus Regional Research Institute

Columbus, Ohio, United States

Location

Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Nephrology

Gabrovo, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Dr. Stamen Iliev", Montana, Department of Nephrology and Dialysis

Montana, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic

Pleven, Bulgaria

Location

Multiprofile Hospital for Active Treatment, Ruse, Department of Urology

Rousse, Bulgaria

Location

Multiprofile Hospital for Active Treatment, Sofia at Military Medical Academy, General Urology Clinic

Sofia, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Aleksandrovska", Sofia, Department of Laparoscopic Urology

Sofia, Bulgaria

Location

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic

Sofia, Bulgaria

Location

Multiprofile Regional Hospital for Active Treatment "Dr. Stefan Cherkezov", Veliko Tarnovo, Department of Urology

Veliko Tarnovo, Bulgaria

Location

Fundacion Cardiomet

Armenia, Colombia

Location

De la Costa Clinic. Ltd. Research Centre

Barranquilla, Colombia

Location

University Hospital Brno, Clinic of Urology

Brno, Czechia

Location

University Hospital Hradec Kralove, Clinic of Urology

Hradec Králové, Czechia

Location

Hospital Novy Jicin, Department of Urology

Nový Jičín, Czechia

Location

University Hospital Olomouc

Olomouc, Czechia

Location

Thomayer Hospital, Department of Urology

Prague, Czechia

Location

East Viru Central Hospital, Surgery Clinic

Kohtla-Järve, Estonia

Location

East Tallinn Central Hospital, Department of Internal Medicine

Tallinn, Estonia

Location

West Tallinn Central Hospital, Department of Urology

Tallinn, Estonia

Location

Tartu University Hospital, Surgery Clinic, Department of Urology and Renal Transplantation

Tartu, Estonia

Location

Western Georgia National Medical Center

Kutaisi, Georgia

Location

Aversi Clinic

Tbilisi, Georgia

Location

Modern Medical Technologies - Guram Karazanashvili's clinic

Tbilisi, Georgia

Location

Research Institute of Clinical Medicine

Tbilisi, Georgia

Location

Tsulukidze National Center of Urology

Tbilisi, Georgia

Location

Evaggelismos Hospital

Kolonaki, Greece

Location

Papageorgiou General Hospital

Thessaloniki, Greece

Location

Principal SMO Kft.

Baja, Hungary

Location

Jahn Ferenc South Pest Hospital, Department of Urology

Budapest, Hungary

Location

Petz Aladar County Teaching Hospital, Department of Urology

Győr, Hungary

Location

Elisabeth Teaching Hospital and Rehabilitation Institute of Sopron, Department of Urology

Sopron, Hungary

Location

Csongrad County Dr. Bugyi Istvan Hospital, Department of Urology

Szentes, Hungary

Location

St. Borbala Hospital, Department of Urology

Tatabánya, Hungary

Location

Zion Medical Center

Haifa, Israel

Location

Hospital Mater Domini

Castellanza, Italy

Location

Liepajas Regional Hospital

Liepāja, Latvia

Location

P. Stradins Clinical University Hospital

Riga, Latvia

Location

Riga East University Hospital, LLC

Riga, Latvia

Location

SIA 'URO' Clinic

Riga, Latvia

Location

Vidzemes Hospital

Valmiera, Latvia

Location

Hospital Civil Fray Antonio Alcalde

Guadalajara, Mexico

Location

Hospital Civil Guadalajara Dr. Juan I. Mendoza

Guadalajara, Mexico

Location

National Scientific Practical Center for Emergency Medicine, Department of Urology

Chisinau, Moldova

Location

Republican Clinical Hospital, Department of Urology

Chisinau, Moldova

Location

Boni Fratres Catoviensis Sp. z o.o., Department of Internal Diseases with Cardiologic Diagnostics Unit

Katowice, Poland

Location

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

Lodz, Poland

Location

Medicome Sp. z o.o.

Oświęcim, Poland

Location

HEUREKA Hanna Szalecka

Piaseczno, Poland

Location

Pope John Paul 2nd Independent Public Provincial Hospital

Zamość, Poland

Location

Emergency Clinical County Hospital Brasov

Brasov, Romania

Location

"Prof. Dr. Th. Burghele" Clinical Hospital

Bucharest, Romania

Location

Delta Hospital

Bucharest, Romania

Location

Craiova Emergency Clinical County Hospital

Craiova, Romania

Location

Clinical Hospital "Dr. C. I. Parhon"

Iași, Romania

Location

Oradea Clinical Municipal Hospital "Dr. Gavril Curteanu"

Oradea, Romania

Location

Sibiu County Emergency Clinical Hospital

Sibiu, Romania

Location

Central Clinical Hospital of Civil Aviation

Moscow, Russia

Location

City Clinical Hospital #57 under Moscow Healthcare Department

Moscow, Russia

Location

Federal Clinical Center for High Medical Technologies

Moscow, Russia

Location

City Clinical Hospital of Emergency Care #2

Novosibirsk, Russia

Location

Penza Regional Clinical Hospital n.a. N.N. Burdenko

Penza, Russia

Location

Rostov State Medical University

Rostov-on-Don, Russia

Location

North-Western State Medical University n.a. I.I. Mechnikov

Saint Petersburg, Russia

Location

Saint-Petersburg Scientific Research Institute for Phthisiopulmonology

Saint Petersburg, Russia

Location

St. Petersburg Clinical Hospital under the Russian Academy of Sciences

Saint Petersburg, Russia

Location

St. Petersburg State Healthcare Institution: City Hospital #15

Saint Petersburg, Russia

Location

St. Petersburg State Healthcare Institution: St. George the Martyr City Hospital

Saint Petersburg, Russia

Location

St. Petersburg State-Funded Healthcare Institution: City Hospital #26

Saint Petersburg, Russia

Location

Saratov State Medical University n.a. V.I. Razumovsky

Saratov, Russia

Location

Smolensk Regional Clinical Hospital

Smolensk, Russia

Location

Novgorod Regional Clinical Hospital

Veliky Novgorod, Russia

Location

Vsevolozhsk Clinical Central District Hospital

Vsevolozhsk, Russia

Location

Lakeview Hospital

Benoni, South Africa

Location

Clinresco Centres

Kempton Park, South Africa

Location

Mzansi Ethical Research Centre

Middleburg, South Africa

Location

St. Georges Hospital

Port Elizabeth, South Africa

Location

Regional Municipal Institution "Chernivtsi Regional Hospital"

Chernivtsi, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipropetrovsk, Ukraine

Location

Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital

Dnipropetrovsk, Ukraine

Location

Ivano-Frankivsk City Clinical Hospital #1

Ivano-Frankivsk, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, Ukraine

Location

O.I. Meschaninov Clinical Hospital of Emergency and Urgent Medical Care

Kharkiv, Ukraine

Location

Shapoval Regional Clinical Center of Urology and Nephrology

Kharkiv, Ukraine

Location

Khmelnytskyi Regional Hospital

Khmelnytskyi, Ukraine

Location

Institute of Urology

Kyiv, Ukraine

Location

Volyn Regional Clinical Hospital

Lutsk, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, Ukraine

Location

Mykolaiv Regional Hospital, Center for Nephrology and Dialysis

Mykolaiv, Ukraine

Location

City Clinical Hospital #10, Urology Department #1

Odesa, Ukraine

Location

Odesa Regional Clinical Hospital

Odesa, Ukraine

Location

Poltava M.V. Sklifosovskyi Regional Clinical Hospital

Poltava, Ukraine

Location

State Institution: Uzhhorod Railway Station Clinical Hospital under State Territorial Industry-Specific Association:Lviv Railway

Uzhhorod, Ukraine

Location

Vinnytsia M.I. Pyrohov Regional Clinical Hospital

Vinnytsia, Ukraine

Location

Municipal Institution "Zaporizhzhia Reqional Clinical Hospital" of Zaporizhzhia Regional Councill

Zaporizhzhya, Ukraine

Location

MeSH Terms

Interventions

eravacycline; Levofloxacin

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Development Officer
• Organization: La Jolla Pharmaceutical Company

ljpcregulatory@ljpc.com

617-715-3600

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 8, 2013
• Study Start: October 6, 2014
• Primary Completion: June 3, 2015
• Study Completion: August 21, 2015
• Last Updated: January 11, 2022
• Results First Posted: December 11, 2018

Record last verified: 2021-12

Locations

HU (6); BU (8); US (6); ES (4); GE (5); IL (1); CZ (5); ZA (4); CO (2); RO (7); UA (18); PL (5); LA (5); ME (2); RU (16); MO (2); GR (2); IT (1)