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

NCT03032510 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: TP-434-021
• Study Type: interventional
• Target: 1,205
• Locations: 12 countries
• Sites: 69

Brief Summary

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).

Conditions

Complicated Urinary Tract Infections

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  TOC visit (14-17 days after randomization)

Secondary Outcomes (1)

• Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit

  TOC visit (14-17 days after randomization)

Study Arms (2)

Eravacycline (Intravenous)/Levofloxacin (Oral)

EXPERIMENTAL

Drug: Eravacycline; Drug: Placebo; Drug: Levofloxacin

Ertapenem (Intravenous)/Levofloxacin (Oral)

ACTIVE COMPARATOR

Drug: Ertapenem; Drug: Placebo; Drug: Levofloxacin

Interventions

Eravacycline DRUG

Also known as: TP-434

Eravacycline (Intravenous)/Levofloxacin (Oral)

Ertapenem DRUG

Also known as: Invanz

Ertapenem (Intravenous)/Levofloxacin (Oral)

Placebo DRUG

Eravacycline (Intravenous)/Levofloxacin (Oral); Ertapenem (Intravenous)/Levofloxacin (Oral)

Levofloxacin DRUG

Also known as: Levaquin

Eravacycline (Intravenous)/Levofloxacin (Oral); Ertapenem (Intravenous)/Levofloxacin (Oral)

Eligibility Criteria

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

You may qualify if:

• Male or female participant with either:
• Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), or
• cUTI with at least one of the following conditions associated with a risk for developing cUTI:
• Indwelling urinary catheter
• Urinary retention (at least approximately 100 milliliters (mL) of residual urine after voiding)
• History of neurogenic bladder
• Partial obstructive uropathy (for example, nephrolithiasis, bladder stones, and ureteral strictures)
• Azotemia of renal origin (not congestive heart failure \[CHF\] or volume related) such that the serum blood urea nitrogen \[BUN\] is elevated (\>20 milligrams \[mg\]/deciliters \[dL\]) and the serum BUN:creatinine ratio is \<15
• Surgically modified or abnormal urinary tract anatomy (for example, bladder diverticula, redundant urine collection system) except urinary tract surgery within the last 30 days (placing of stents or catheters is not considered to be surgical modification)
• At least 18 years of age at time of consent
• Able to provide informed consent
• At least two of the following signs or symptoms:
• Chills, rigors, or warmth associated with fever or hypothermia
• Flank pain (pyelonephritis) or pelvic pain (cUTI)
• Nausea or vomiting

You may not qualify if:

• Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment except under the following circumstances:
• Participants with suspected acute cUTI who have received a single dose of effective non-study antibiotics for the acute cUTI
• Signs and symptoms of cUTI developed while on the antibiotic for another indication
• History of an ertapenem-resistant urinary tract infection within 1 year of enrollment
• Likely to require \>10 days of antibiotic treatment to cure the acute cUTI or likely to receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28 days after randomization) \[for example, participants with chronic vesiculo-ureteral reflux\]
• Unlikely to survive at least through the duration of the study
• Hypotension, systolic blood pressure ≤90 millimeters of mercury \[mmHg\]
• Complicated pyelonephritis with complete obstruction or known or suspected renal or perinephric abscess, emphysematous pyelonephritis, or Any condition likely to require surgery to achieve cure (this does not include procedure to place catheters or obtain diagnosis)
• Known or suspected urinary fungal infection
• Uncomplicated lower urinary tract infections
• Suspected or confirmed active prostatitis, or currently under treatment for prostatitis
• High risk for cUTI due to Pseudomonas (for example, history of prior cUTIs due to Pseudomonas, ≥20 mg once a day prednisone or equivalent steroid, and other risk factors as perceived by the Investigator)
• History of renal transplantation
• Presence of an ileal loop
• Any history of trauma to the pelvis or urinary tract occurring within 30 days of screening

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead

Study Sites (69)

Unknown Facility

Fullerton, California, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Torrance, California, United States

Location

Unknown Facility

Coral Gables, Florida, United States

Location

Unknown Facility

Doral, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Columbus, Georgia, 31820, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Las Vegas, Nevada, United States

Location

Unknown Facility

Baytown, Texas, United States

Location

Unknown Facility

Graz, Austria

Location

Unknown Facility

Linz, Austria

Location

Unknown Facility

Salzburg, Austria

Location

Unknown Facility

Pleven, Bulgaria

Location

Unknown Facility

Plovdiv, Bulgaria

Location

Unknown Facility

Razgrad, Bulgaria

Location

Unknown Facility

Rousse, Bulgaria

Location

Unknown Facility

Smyadovo, Bulgaria

Location

Unknown Facility

Sofia, Bulgaria

Location

Unknown Facility

Varna, Bulgaria

Location

Unknown Facility

Veliko Tarnovo, Bulgaria

Location

Unknown Facility

Tallinn, Estonia

Location

Unknown Facility

Tartu, Estonia

Location

Unknown Facility

Võru, Estonia

Location

Unknown Facility

K'ut'aisi, Georgia

Location

Unknown Facility

Tbilisi, Georgia

Location

Unknown Facility

Baja, Hungary

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Miskolc, Hungary

Location

Unknown Facility

Nagykanizsa, Hungary

Location

Unknown Facility

Nyíregyháza, Hungary

Location

Unknown Facility

Sopron, Hungary

Location

Unknown Facility

Szentes, Hungary

Location

Unknown Facility

Tatabánya, Hungary

Location

Unknown Facility

Jelgava, Latvia

Location

Unknown Facility

Riga, Latvia

Location

Unknown Facility

Valmiera, Latvia

Location

Unknown Facility

Chisinau, Moldova

Location

Unknown Facility

Brasov, Romania

Location

Unknown Facility

Bucharest, Romania

Location

Unknown Facility

Craiova, Romania

Location

Unknown Facility

Oradea, Romania

Location

Unknown Facility

Arkhangelsk, Russia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Pyatigorsk, Russia

Location

Unknown Facility

Rostov-on-the-Don, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Smolensk, Russia

Location

Unknown Facility

Vsevolozhsk, Russia

Location

Unknown Facility

Yaroslavl, Russia

Location

Unknown Facility

Nitra, Slovakia

Location

Unknown Facility

Poprad, Slovakia

Location

Unknown Facility

Prešov, Slovakia

Location

Unknown Facility

Svidník, Slovakia

Location

Unknown Facility

Žilina, Slovakia

Location

Unknown Facility

Chernihiv, Ukraine

Location

Unknown Facility

Chernivtsi, Ukraine

Location

Unknown Facility

Dnipro, Ukraine

Location

Unknown Facility

Ivano-Frankivsk, Ukraine

Location

Unknown Facility

Kharkiv, Ukraine

Location

Unknown Facility

Kyiv, Ukraine

Location

Unknown Facility

Lviv, Ukraine

Location

Unknown Facility

Mykolaiv, Ukraine

Location

Unknown Facility

Odesa, Ukraine

Location

Unknown Facility

Poltava, Ukraine

Location

Unknown Facility

Uzhhorod, Ukraine

Location

Unknown Facility

Vinnytsia, Ukraine

Location

Unknown Facility

Zaporizhia, Ukraine

Location

Unknown Facility

Zhytomyr, Ukraine

Location

MeSH Terms

Interventions

eravacycline; Ertapenem; Levofloxacin

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

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

ljpcregulatory@ljpc.com

617-715-3600

Study Officials

• Chief Medical Officer

  Tetraphase Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: January 26, 2017
• Study Start: January 1, 2017
• Primary Completion: December 1, 2017
• Study Completion: January 1, 2018
• Last Updated: January 6, 2022
• Results First Posted: October 2, 2019

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); BU (8); ES (3); LA (3); RU (8); HU (8); GE (2); MO (1); SL (5); RO (4); UA (14); AU (3)