[Translation] A randomized, double-blind, multicenter, phase 3 study to determine the efficacy and safety of cefepime-zidebactam versus meropenem in the treatment of adult subjects with complicated urinary tract infection or acute pyelonephritis

主要目的：证明头孢吡肟-zidebactam（FEP-ZID）在以下方面非劣效于美罗培南：检查治愈情况（TOC）访视时微生物学改良的意向治疗（mMITT）人群中的总体成功率（临床治愈+微生物根除率）; 评估FEP-ZID在安全性人群中的总体安全性和耐受性; 次要目的：评价TOC时临床可评价（CE）和微生物学可评价（ME）人群中的总体疗效; 评价治疗结束（EOT）时mMITT人群中的总体疗效; 评价EOT（mMITT人群）和TOC（mMITT、CE和ME人群）时的临床结果; 评价EOT（mMITT人群）和TOC（mMITT、CE和ME人群）时的微生物学结果; 评价TOC时按致病菌划分的总体疗效（mMITT、CE和ME人群）以及按致病菌划分的临床结果（mMITT和CE人群）和微生物学结果（mMITT和ME人群）; 评价后期随访（LFU）时mMITT人群的临床结果; 评价FEP-ZID用于治疗复杂性尿路感染（cUTI）或急性肾盂肾炎（AP）成人受试者时的药代动力学（PK）;

[Translation]

Primary objectives: To demonstrate that cefepime-zidebactam (FEP-ZID) is non-inferior to meropenem in terms of: Overall success rate (clinical cure + microbiological eradication rate) in the microbiological modified intention-to-treat (mMITT) population at the check-of-cure (TOC) visit; To assess the overall safety and tolerability of FEP-ZID in the safety population; Secondary objectives: To assess the overall efficacy in the clinically evaluable (CE) and microbiologically evaluable (ME) populations at TOC; To assess the overall efficacy in the mMITT population at the end of treatment (EOT); To assess the overall efficacy of FEP-ZID in the EOT (mMITT population) and TOC (mM =To evaluate the clinical outcomes at EOT (mMITT population) and TOC (mMITT, CE and ME populations); To evaluate the overall efficacy by pathogen at TOC (mMITT, CE and ME populations) and the clinical outcomes (mMITT and CE populations) and microbiological outcomes (mMITT and ME populations) by pathogen; To evaluate the clinical outcomes in the mMITT population at late follow-up (LFU); To evaluate the pharmacokinetics (PK) of FEP-ZID in adult subjects with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP);

Start Date25 May 2024

Sponsor / Collaborator

Wockhardt Bio AG

[+2]

CTR20233796 / CompletedPhase 1

一项在中国健康受试者中评价FEP-ZID的药代动力学、安全性和耐受性的随机、双盲、安慰剂对照、单次给药I期研究

[Translation] A randomized, double-blind, placebo-controlled, single-dose phase I study to evaluate the pharmacokinetics, safety, and tolerability of FEP-ZID in healthy Chinese subjects

本研究的主要目的是：在中国健康受试者中评价3 g头孢吡肟-zidebactam（FEP-ZID）单次静脉注射（IV）给药的药代动力学（PK）。本研究的次要目的是：在中国健康受试者中评价3 g FEP-ZID单次IV给药的安全性和耐受性。

[Translation]

The primary objectives of this study are: To evaluate the pharmacokinetics (PK) of a single intravenous (IV) dose of 3 g cefepime-zidebactam (FEP-ZID) in healthy Chinese subjects. The secondary objectives of this study are: To evaluate the safety and tolerability of a single IV dose of 3 g FEP-ZID in healthy Chinese subjects.

Start Date10 May 2024

Sponsor / Collaborator

Wockhardt Bio AG

[+2]

NCT04979806 / RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Multicenter, Comparative Study to Determine the Efficacy and Safety of Cefepime-zidebactam vs. Meropenem in the Treatment of Complicated Urinary Tract Infection or Acute Pyelonephritis in Adults

This is a Phase 3, randomized, double-blind, multicenter, non-inferiority study to evaluate the efficacy, safety, and tolerability of FEP-ZID vs. meropenem in the treatment of hospitalized adults with cUTI or AP.
Approximately 528 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. The total duration of treatment with study drug is 7 to 10 days. Each subject must remain hospitalized during the study drug treatment period; no outpatient parenteral antibiotic therapy is allowed.

Start Date28 Aug 2022

Sponsor / Collaborator

Wockhardt Ltd.

[+1]

100 Clinical Results associated with Cefepime/Zidebactam

100 Translational Medicine associated with Cefepime/Zidebactam

100 Patents (Medical) associated with Cefepime/Zidebactam

Literatures (Medical) associated with Cefepime/Zidebactam

29 Jun 2022·JOURNAL OF ANTIMICROBIAL CHEMOTHERAPYQ2 · MEDICINE

Inoculum effects of cefepime/zidebactam (WCK 5222) and ertapenem/zidebactam (WCK 6777) for Enterobacterales in relation to β-lactamase type and enhancer effect, as tested by BSAC agar dilution

Q2 · MEDICINE

Article

Author: Woodford, Neil ; Chaudhry, Aiysha ; Livermore, David M ; Vickers, Anna ; Mushtaq, Shazad

Abstract:

Objectives:

Combinations of PBP3-active β-lactams with developmental diazabicyclooctanes (DBOs), e.g. zidebactam, remain active against many MBL producers via an enhancer effect. We explored how this activity is affected by inoculum.

Materials and methods:

MICs of zidebactam and its cefepime and ertapenem combinations (WCK 5222 and WCK 6777, respectively) were determined by BSAC agar dilution at inocula from 3–6 × 103 to 3–6 × 105 cfu/spot. Isolates, principally Klebsiella spp., were chosen as having previously tested resistant to zidebactam or its cefepime combination, and by β-lactamase type.

Results:

MICs of zidebactam, tested alone, were strongly inoculum dependent regardless of β-lactamase type; MICs of its cefepime and ertapenem combinations likewise were strongly inoculum dependent—rising ≥32-fold across the inoculum range tested—but only for MBL producers. Combination MICs for isolates with non-MBLs, including those with OXA-48 (where the enhancer effect remains critical for ertapenem/zidebactam) were much less inoculum dependent, particularly for cefepime/zidebactam. MBL producers frequently moved between putative ‘susceptible’ (MIC ≤ 8 + 8 mg/L) and ‘resistant’ (MIC > 8 + 8 mg/L) categories according to whether the inoculum was at the high or low end of BSAC’s acceptable (1–4 × 104 cfu/spot) range.

Conclusions:

The activity of zidebactam combinations against MBL producers, which strongly depends on the enhancer effect, is inoculum dependent. Animal data suggest consistent in vivo activity even in high-inoculum pneumonia models. Contingent on this being supported by clinical experience, the combination behaviour may be best represented by the MICs obtained at the lower end of BSAC’s inoculum range.

23 Feb 2022·Microbiology spectrumQ2 · BIOLOGY

Molecular Characterization of WCK 5222 (Cefepime/Zidebactam)-Resistant Mutants Developed from a Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolate

Q2 · BIOLOGY

Article

Author: Zhao, Xinrui ; Cheng, Zhihui ; Bai, Fang ; Wu, Weihui ; Ren, Huan ; Song, Yuqin ; Liang, Qi’an ; Feng, Jie ; Tian, Zhenyang ; Pan, Xiaolei ; Jin, Yongxin

Antibiotic resistance imposes a severe threat on human health. WCK 5222 is a β-lactam/β-lactamase inhibitor combination that is composed of cefepime and zidebactam.

12 Aug 2021·The Journal of antimicrobial chemotherapyQ2 · MEDICINE

Comparative in vivo activity of human-simulated plasma and epithelial lining fluid exposures of WCK 5222 (cefepime/zidebactam) against KPC- and OXA-48-like-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model

Q2 · MEDICINE

Article

Author: Lasko, Maxwell J. ; Nicolau, David P. ; Abdelraouf, Kamilia

Abstract:

Objectives:

This was a comparative assessment of WCK 5222 (cefepime/zidebactam 2/1 g as a 1 h infusion every 8 h) efficacy using human-simulated plasma and ELF exposures against serine-carbapenemase-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model.

Methods:

Ten clinical isolates were utilized: eight were serine-carbapenemase-producing (KPC, n = 4; OXA-48-like, n = 4) Enterobacterales with WCK 5222 MICs (1:1) ranging from 1 to 4 mg/L; and two were previously studied MDR isolates serving as quality controls. Lungs of mice were inoculated with 50 μL of 107 cfu/mL. Treatment mice received human-simulated regimens of cefepime, zidebactam or WCK 5222 derived from plasma or epithelial lining fluid (ELF) profiles obtained from healthy subjects. Lung bacterial densities resulting from the humanized exposures in plasma and ELF were compared.

Results:

Initial lung bacterial densities ranged from 6.06 to 6.87 log10 cfu/lungs, with a mean bacterial burden increase to 9.06 ± 0.42 after 24 h. Human-simulated plasma and ELF exposures of cefepime and zidebactam monotherapy had no activity. Human-simulated WCK 5222 plasma exposures resulted in a >1 log10 cfu/lungs reduction in bacterial burden for all isolates. Humanized WCK 5222 ELF exposures achieved a >1 log10 cfu/lungs reduction for all isolates. While statistically significant differences in bacterial burden reduction were observed between the plasma and ELF exposures for WCK 5222 in 5/8 isolates, all treatments achieved the translational kill target of a >1 log10 cfu reduction.

Conclusions:

Clinically achievable WCK 5222 plasma and ELF exposures produced in vivo killing of carbapenem-resistant Enterobacterales in the neutropenic murine pneumonia model that is predictive of efficacy in humans.

100 Deals associated with Cefepime/Zidebactam

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute pyelonephritis	Phase 3	US	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	CN	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	BG	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	EE	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	IN	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	LT	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	MX	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	PE	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	PL	Wockhardt Ltd.	28 Aug 2022
Complicated urinary tract infection	Phase 3	US	Wockhardt Ltd.	28 Aug 2022

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