Delving into the Latest Updates on Cefepime/Zidebactam with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Zidebactam/cefepime intravenous

Target

PBP3

Action

inhibitors

Mechanism

PBP3 inhibitors(Penicillin-binding protein 3 inhibitors), Cell wall inhibitors

Therapeutic Areas

Infectious DiseasesUrogenital Diseases

Active Indication

Acute pyelonephritisComplicated urinary tract infection

Inactive Indication

Gram-Negative Bacterial InfectionsPseudohypoaldosteronism

Originator Organization

Wockhardt Ltd.

Active Organization

Wockhardt Ltd.

ACS Dobfar SpA

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC13H21N5O7S

InChIKeyYCZPXRQPDCXTIO-BBBLOLIVSA-N

CAS Registry1436861-97-0

View All Structures (2)

This is a Phase I, Single-Center, Open-Label study evaluating the safety and pharmacokinetics of single doses of ZID-FEP and metronidazole alone or in combination utilizing a 3-period, crossover study design. Thirty eligible male and female healthy adult subjects will participate in the study and receive single doses of (1) ZID-FEP 3g IV (ZID 1 g plus FEP 2 g) administered over 1 hour (h); (2) metronidazole 0.5 g IV alone administered over 1 h; and (3) metronidazole 0.5 g IV over 1 h, followed by ZID-FEP 3g IV over 1 h over 3 treatment periods separated by a 48 h washout period.

Start Date27 Jan 2025

Sponsor / Collaborator

Wockhardt Ltd.

CTR20222627

/ Active, not recruitingPhase 3

一项在复杂性尿路感染或急性肾盂肾炎成人受试者治疗中确定头孢吡肟-zidebactam与美罗培南的有效性和安全性的随机、双盲、多中心的3期对比研究

[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]

100 Clinical Results associated with Cefepime/Zidebactam

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100 Translational Medicine associated with Cefepime/Zidebactam

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100 Patents (Medical) associated with Cefepime/Zidebactam

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19

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

AbstractObjectivesCombinations 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 methodsMICs 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.ResultsMICs 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.ConclusionsThe 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.

01 Jun 2022·Biomedical Chromatography

Ensuring robustness in the quality of antibiotic susceptibility test discs for four novel antibiotics

Article

Author: Yeole, Ravindra D. ; Bhagwat, Sachin S. ; Vaidya, Suyog N. ; Patel, Mahesh V. ; Ahirrao, Vinod K. ; Jadhav, Rajiv A.

AbstractAntibiotic susceptibility test (AST) discs are used as an in‐vitro diagnostic tool to select the appropriate antibiotic to treat an infection. Generally, the concentration of the drug loaded on to the AST discs is measured by studying its activity against quality control organisms. This methodology has several limitations—it is time consuming, requires trained manpower, has a wider acceptance criteria of zone of inhibitions—causing ambiguity in judging smaller variations in drug concentration. To overcome these issues, we have developed and validated high‐performance liquid chromatographic (HPLC) methods for the determination of strength of AST discs for in‐house researched antibiotics, namely Levonadifloxacin/WCK 771, Nafithromycin/WCK 4873, Cefepime‐Tazobactam/WCK 4282, and Cefepime‐Zidebactam/WCK 5222. The drugs were extracted from the AST discs using an appropriate solvent. The developed methods are simple, accurate, precise, reproducible, rugged, and robust. They are efficient in terms of time, and can be easily conducted in a quality control laboratory during release as well as stability evaluation of AST disc. Application of HPLC methods for the determination of strength of AST discs ensures flawless quality and, consequently, a better selection of drugs to treat bacterial infections in clinics.

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

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.

100 Deals associated with Cefepime/Zidebactam

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute pyelonephritis	Phase 3	Bulgaria	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	India	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	China	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	Mexico	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	Slovakia	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	Estonia	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	Poland	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	United States	Wockhardt Ltd.	28 Aug 2022
Acute pyelonephritis	Phase 3	Lithuania	Wockhardt Ltd.	28 Aug 2022
Complicated urinary tract infection	Phase 3	China	Wockhardt Ltd.	28 Aug 2022