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

Phase 2

Completed

• Conditions: Complicated Urinary Tract Infection; Acute Pyelonephritis
• Interventions: Drug: Sulbactam-ETX2514; Drug: Placebo; Drug: Imipenem-cilastatin

• Registration Number: NCT03445195
• Lead Sponsor: Entasis Therapeutics

Brief Summary

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.

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 Timeline

• Study Start: 2018-01-17
• Study First Submitted: 2018-02-20
• Study First Submitted QC: 2018-02-20
• Study First Posted: 2018-02-26
• Primary Completion: 2018-05-17
• Study Completion: 2018-05-17
• Results First Submitted: 2019-05-14
• Results First Submitted QC: 2019-05-14
• Status Verified: 2019-06
• Results First Posted: 2019-06-05
• Last Update Submitted: 2020-01-20
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin	Sulbactam-ETX2514	-
Placebo + Imipenem/Cilastatin	Placebo	-
Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin	Imipenem-cilastatin	-
Placebo + Imipenem/Cilastatin	Imipenem-cilastatin	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Overall Success	From baseline through day 21	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.

Secondary Outcome Measures

Name	Time	Method
Microbiologic Eradication	Baseline to day 21	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
Clinical Cure	Baseline to day 21	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.

Trial Locations

Locations (4)

Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Doverie; 🇧🇬 Sofia, Bulgaria

Universeity Multiprofile Hospital for Active Teatment; 🇧🇬 Sofia, Bulgaria

University Multiprofile Hospital for Active Teatment-Clinic of Nephrology; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Teatment (MHAT) and Emergency Medicine - Pirogov; 🇧🇬 Sofia, Bulgaria