Evaluation of Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis

This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy.

Study Overview

• Status: Completed
• Conditions: Acute Pyelonephritis; Complicated Urinary Tract Infection
• Intervention / Treatment: Drug: Sulbactam-ETX2514; Drug: Imipenem-cilastatin; Drug: Placebo

Detailed Description

This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs who are otherwise relatively healthy. Patients with Acute Pyelonephritis may also be enrolled. Approximately 80 patients will be randomized to receive either 1 g ETX2514/1 g sulbactam IV or matching placebo every 6 hours (q6h). All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1431
    • Universeity Multiprofile Hospital for Active Teatment
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Teatment-Clinic of Nephrology
  • Sofia, Bulgaria, 1606
    • Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Pirogov
  • Sofia, Bulgaria, 1632
    • Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Doverie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient as permitted by local law and institutional Standard Operating Procedures.
• Male or female, 18 to 90 years of age, inclusive.
• Expectation, in the judgment of the Investigator, that the patient's cUTI would require initial hospitalization and treatment with IV antibiotics.
• Documented or suspected cUTI or Acute pyelonephritis (AP).

Exclusion Criteria:

• Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter.
• Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization that would interfere with evaluation of response to the study antibiotics.
• Patient requires continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study.
• Receipt of a single dose of a long-acting, potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization.
• Requirement at time of randomization for any reason for additional systemic antimicrobial therapy (including antibacterial, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis.
• Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study [from randomization through the Late Follow-up (LFU) Visit].
• Any patients previously randomized in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin	Drug: Sulbactam-ETX2514; The ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h.; Other Names: ETX2514SUL; Drug: Imipenem-cilastatin; All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
Placebo Comparator: Placebo + Imipenem/Cilastatin	Drug: Imipenem-cilastatin; All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.; Drug: Placebo; Matching 1g IV solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Success	The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit.	From baseline through day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure	Proportion of patients with a response of clinical cure for the MITT(modified intent to treat), m-MITT (microbiologically modified intent to treat), CE(clinically evaluable), and ME(microbiologically evaluable) populations at the TOC(test of cure) visit.	Baseline to day 21
Microbiologic Eradication	Proportion of patients with a response of microbiologic eradication for the m-MITT(microbiologically modified intent to treat) and ME(microbiologically evaluable) populations at the TOC visit	Baseline to day 21

Collaborators and Investigators

• Sponsor: Entasis Therapeutics
• Investigators: Study Chair: Anibal Calmaggi, MD, Medpace, Inc.

Publications and helpful links

General Publications

• Sagan O, Yakubsevitch R, Yanev K, Fomkin R, Stone E, Hines D, O'Donnell J, Miller A, Isaacs R, Srinivasan S. Pharmacokinetics and Tolerability of Intravenous Sulbactam-Durlobactam with Imipenem-Cilastatin in Hospitalized Adults with Complicated Urinary Tract Infections, Including Acute Pyelonephritis. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01506-19. doi: 10.1128/AAC.01506-19. Print 2020 Feb 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2018
• Primary Completion (Actual): May 17, 2018
• Study Completion (Actual): May 17, 2018

Study Registration Dates

• First Submitted: February 20, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 20, 2020
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Nephritis, Interstitial; Pyelitis; Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Imipenem; Cilastatin; Sulbactam; Cilastatin, Imipenem Drug Combination
• Other Study ID Numbers: CS2514-2017-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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