Study of Cefepime-tazobactam (FEP-TAZ) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

A Phase III, Randomized, Double-Blind, Multicenter, Comparative Study to Determine the Efficacy and Safety of Cefepime-Tazobactam vs. Meropenem Followed by Optional Oral Therapy in the Treatment of Complicated Urinary Tract Infection or Acute Pyelonephritis in Adults

This is a Phase III, randomized, double-blind, multicenter, non-inferiority study to evaluate the efficacy, safety, and tolerability of FEP-TAZ vs. meropenem in the treatment of hospitalized adults with cUTI or AP.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Pyelonephritis; Complicated Urinary Tract Infection
• Intervention / Treatment: Drug: WCK 4282 (FEP-TAZ) 4 g; Drug: ciprofloxacin 500 mg Optional Oral Switch; Drug: Meropenem; Other: Infusion of normal saline

Detailed Description

Approximately 1004 hospitalized adult subjects (≥18 years of age) diagnosed with cUTI or AP will be enrolled in the study. The diagnosis of cUTI or AP will be based on a combination of clinical symptoms and signs plus the presence of pyuria

Subjects will be randomized in a 1:1 ratio according to an Interactive Response Technology (IRT) electronic system to receive either FEP-TAZ 4 g (2 g cefepime + 2 g tazobactam) IV every eight hours (q8h) or meropenem 1 g IV q8h. FEP-TAZ will be administered as 2 consecutive infusions of 2 g (1 g cefepime + 1 g tazobactam)

• Study Type: Interventional
• Enrollment (Estimated): 1004
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Manishkumar D Shah, PhD; Phone Number: 6308 91-22-26596000; Email: Manish.Shah@wockhardt.com
• Study Contact Backup: Name: Mugdha A Gupta, MMS; Phone Number: 6355 91-22-26596000; Email: mgupta@wockhardt.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Meet the following clinical criteria for either cUTI or AP:

A. cUTI:

1. Have at least TWO of the following new-onset or worsening symptoms or signs:

   Fever (oral, tympanic, or rectal temperature >38°C [>100.4°F]), which must be observed and documented by a health care provider Nausea or vomiting Dysuria, increased urinary frequency, or urinary urgency Lower abdominal, suprapubic, or pelvic pain

2. Have at least ONE complicating factor

B. AP, defined as acute flank pain (onset within 7 days prior to randomization) or costovertebral angle tenderness on physical examination, plus at least ONE of the following new-onset or worsening symptoms or signs:

3. Evidence of pyuria within 48 h prior to randomization,

Exclusion Criteria:

1. Known or suspected disease or condition that, in the opinion of the investigator, may confound the assessment of efficacy.
2. Receipt of potentially-effective systemic antibacterial therapy within 72 h prior to randomization
3. Rapidly progressive or terminal illness with a high risk of mortality due to any cause, including but not limited to acute hepatic failure, respiratory failure, or septic shock, such that the subject is unlikely to survive the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WCK 4282 (FEP-TAZ) 4 g; WCK 4282 (FEP-TAZ) Pharmaceutical dosage form: Intravenous infusion Dosage: 4 g (2 g FEP and 2 g TAZ) IV q8h, infused over 90 min	Drug: WCK 4282 (FEP-TAZ) 4 g; WCK 4282 (FEP-TAZ) 4 g [2 g FEP and 2 g TAZ] IV q8h, infused over 90 min; Drug: ciprofloxacin 500 mg Optional Oral Switch; ciprofloxacin 500 mg PO q12h
Active Comparator: Meropenem; Meropenem Pharmaceutical dosage form: Intravenous infusion Dosage: 1 g IV q8h, infused over 45 min	Drug: ciprofloxacin 500 mg Optional Oral Switch; ciprofloxacin 500 mg PO q12h; Drug: Meropenem; 1 g IV q8h, infused over 45 min; Other: Infusion of normal saline; Infusion of normal saline over 45 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with overall success at Day 5	Overall success is defined as complete resolution (or return to premorbid state) of the cUTI or AP symptoms that were present at screening, except flank pain (if present), which should show at least one grade improvement and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 colony forming units or CFU/mL)	Day 5
Percentage of subjects with overall success at Test-of-Cure	Overall success is defined as complete resolution1 (or return to premorbid state) of the cUTI or AP symptoms that were present at Screening and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 colony forming units or CFU/mL)	Test Of Cure Visit (Day 17 ± 2 days)
Percentage of subjects with Treatment-Emergent Adverse Events (TEAE)	Collection of number of adverse events.	Day 1 to the end of study Late Follow-Up visit (LFU) (26 ± 2 days)

Collaborators and Investigators

• Sponsor: Wockhardt
• Investigators: Study Director: Manishkumar D Shah, PhD, Wockhardt

Publications and helpful links

General Publications

• Isler B, Harris P, Stewart AG, Paterson DL. An update on cefepime and its future role in combination with novel beta-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa. J Antimicrob Chemother. 2021 Feb 11;76(3):550-560. doi: 10.1093/jac/dkaa511.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Nephritis, Interstitial; Pyelitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; 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; Ciprofloxacin; Meropenem
• Other Study ID Numbers: W-4282-301

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