CTRI/2024/04/066014 [Registered on: 19/04/2024] Trial Registered Prospectively
Last Modified On:
26/08/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Study to Determine the Efficacy and Safety of
Cefepime- Tazobactam in the
Treatment of Urinary Tract Infection
Scientific Title of Study
A Phase II/III, Randomized, Double-blind, Multicenter,
Comparative Study to Determine the Efficacy and Safety of
Cefepime- Tazobactam (WCK 4282) vs. Meropenem in the
Treatment of Complicated Urinary Tract Infection or Acute
Pyelonephritis in Adults
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
W-4282-303 Protocol Version 1.0 dated 18 April 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sachin Bhagwat
Designation
Senior Vice President
Affiliation
Wockhardt
Address
Wockhardt Research Centre
Division - Drug Discovery Research Department- Microbiology D-4 MIDC, Chikalthana, Aurangabad
Aurangabad
MAHARASHTRA
Aurangabad MAHARASHTRA 431006 India
Phone
02406694185
Fax
Email
sbhagwat@wockhardt.com
Details of Contact Person Scientific Query
Name
Dr Sachin Bhagwat
Designation
Senior Vice President
Affiliation
Wockhardt
Address
Wockhardt Research Centre
Division - Drug Discovery Research Department- Microbiology D-4 MIDC, Chikalthana, Aurangabad
Aurangabad
MAHARASHTRA
MAHARASHTRA 431006 India
Phone
02406694185
Fax
Email
sbhagwat@wockhardt.com
Details of Contact Person Public Query
Name
Dr Sachin Bhagwat
Designation
Senior Vice President
Affiliation
Wockhardt
Address
Wockhardt Research Centre
Division - Drug Discovery Research Department- Microbiology D-4 MIDC, Chikalthana, Aurangabad
Aurangabad
MAHARASHTRA
MAHARASHTRA 431006 India
Phone
02406694185
Fax
Email
sbhagwat@wockhardt.com
Source of Monetary or Material Support
Wockhardt Research Centre, D-4 MIDC, Chikalthana, Aurangabad-431006, Maharashtra, India
OPD#02, First Floor, Aartham Multi Super Speciality Hospital, Opp Government Polytechnic, L-Colony, Near Panjarapole Cross Road, Ambawadi, Ahmedabad-380006, Gujarat, INDIA. Ahmadabad GUJARAT
9824919119 9824919119 jmvakil@hotmail.com
Dr Prashant Raghunath Potdar
Accord Multispecialty Hospital
Ground Floor, Accord Hospital, Santnagar Sector No. 04, Moshi Pradhikaran, Pune-Nashik Highway, Pune-412105, Maharashtra, INDIA Pune MAHARASHTRA
Ground Floor, Room#11, Department of General Medicine, ACSR Government Medical College and Hospital, Dargamitta, Nellore-524004, Andhra Pradesh, INDIA Nellore ANDHRA PRADESH
Room No 120, Medicine department, B block, first floor, OPD building,All Indian Institute of Medical Sciences (AIIMS), Jodhpur-342005, Rajasthan INDIA.
Jaipur RAJASTHAN
Room No. 01, Ground Floor, Anand Multispeciality Hospital, PMT Chowk, Pune-Nashik Road, Bhosari, Pune- 411039, Maharashtra, INDIA Pune MAHARASHTRA
7030729676 7030729676 upendra31jul@rediffmail.com
Dr Vinish Kumar Singh
Atharva Mutispeciality Hospital and Research Centre
OPD 02, Ground Floor, Atharva Mutispeciality Hospital and Research Centre, H-4 Comm-2, Construction Div-21, UP Avas Vikas Parishad, Sector-E, Lucknow-226003, Uttar-Pradesh, INDIA Lucknow UTTAR PRADESH
7275981480
vinishkumarsingh208@gmail.com
Dr Vijay Kulkarni
Bharati Vidyapeeth (Deemed to be University) Medical College And Hospital
Room#02, Ground floor, Bharati Vidyapeeth (Deemed to be University) Medical College And Hospital, Sangli-Miraj Rd, Wanaleswadi, Sangli-416416 Maharashtra, INDIA Sangli MAHARASHTRA
9740021115
vijayk.07023@gmail.com
Dr Harshalkumar Joshi
Dhiraj Hospital, Sumandeep Vidyapeeth Deemed to be University
OPD#206, Ground Floor, Nephrology Department, Dhiraj Hospital, SBKS MI and RC (Affiliated to SVDU), Sumandeep Vidyapeeth, Deemed to be University, At and PO Piparia, TA Waghodiya, Vadodara-391760, Gujarat, INDIA. Vadodara GUJARAT
9427611847
harshal11joshi@gmail.com
Dr Shankar Tanaji Mundhe
Eras Bharti Hospital
Room#02, Fourth Floor, Eras Bharti Hospital, Ganesham Commercial, A Building, Floor 3rd & 4th, BRT Link Road, Pimple Saudagar, Pune 411027, Maharashtra, INDIA Pune MAHARASHTRA
Room No. 03, Ground Floor, Rhythm Heart Institute- A Unit of SLPL, Near Siddharth Bunglows, Sama- Savli Road, Vadodara – 390022, Gujarat, INDIA Vadodara GUJARAT
9998002055 9998002055 drkedarsuthar@gmail.com
Dr Sanjeev Garg
S.R. Kalla Memorial Gastro and General Hospital
Basement, S.R. Kalla Memorial Gastro and General Hospital 78-79 Dhuleshwar Garden Behind HSBC Bank Sardar Patel Marg C-Scheme Jaipur-302001, Rajasthan, INDIA Jaipur RAJASTHAN
1414039432
drsanjeevgargkalla@gmail.com
Dr Deepakkumar Anandrao Mane
Saikrupa Hospital
First Floor, Room#03,Saikrupa Hospital , Renuka Corner,Tapkir Chowk,Thergaon,Pune 411033
Pune MAHARASHTRA
9371009103
drdmaneresearch@gmail.com
Dr Monica Gupta
Samvedna Hospital
OPD#01, Ground Floor, A-Block, Samvedna Hospital, B 27/88 G, New Colony, Ravindrapuri, Varanasi-221005, Uttar Pradesh, INDIA
Varanasi UTTAR PRADESH
9415336322
monica.samvedna@gmail.com
Dr Dhananjay Vinayak Selukar
Shree Hospital and Critical Care Centre Hospital
First Floor, Shree Hospital and Critical Care Centre Hospital, having its registered office at, Shree Hospital and Critical Care Centre, 799, Om Nagar, Opposite Tajshree Building Sakkardara Square, Nagpur-440009, Maharashtra INDIA. Nagpur MAHARASHTRA
9225234197
dhananjayselokar@yahoo.com
Dr Pratikshit Madhav Mahajan
Supe Heart and Diabetes Hospital and Research Centre
First Floor, Room#03, Supe Heart and Diabetes Hospital and Research Centre, Opp. Adhar Asharam, Near Rungta School, Gharpure Ghat, Ashok Stambh, Nasik-422002, Maharashtra, INDIA Nashik MAHARASHTRA
Victoria Hospital, Bangalore Medical College and Research Institute
Room#67, First Floor,
Victoria Hospital,
Bangalore Medical
College and Research
Institut, Medicine C
Block, Department of
General Medicine,
Victoria Hospital,
BMC & RI, K.R. Road,
Fort, Bangalore
560002, Karnataka,
INDIA. Bangalore KARNATAKA
(1) ICD-10 Condition: N390||Urinary tract infection, site notspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Cefepime-tazobactam (FEP-TAZ)
Dose - Cefepime-tazobactam 4 g (2 g cefepime + 2 g tazobactam)
Route of administration - Intravenous Frequency - Every eight hours Total duration - 7 to 21 days
Comparator Agent
Meropenem
Pharmaceutical dosage form: Intravenous infusion
Route of administration - Intravenous Frequency - Every eight hours Total duration - 7 to 21 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
60.00 Year(s)
Gender
Both
Details
1. Male or female ≥ 18 years old
2. Provide a signed written informed consent prior to any study-specific procedures
3. Meet the following clinical criteria for either cUTI or AP:
A. cUTI:
a. Have at least TWO of the following new-onset or worsening symptoms or signs:
Fever (oral, tympanic, or rectal temperature more than 38°C [more than 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
b. Have at least ONE of the following complicating factors:
-Use of intermittent urethral catheterization or presence of an indwelling urethral catheter (Note: indwelling urethral catheters that have been in place for more than 24 hours prior to Screening must be removed or replaced prior to collection of the screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated)
-Current known functional or anatomical abnormality of the urogenital tract, including anatomic malformations or neurogenic bladder, or with a post-void residual urine volume of more than and equal to 100 mL
-Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to EOT)
-Azotemia, defined as BUN more than 20 mg/dL (or blood urea more than 42.8 mg/dL) or serum creatinine more than 1.4 mg/dL, due to known prior intrinsic renal disease
-Documented history of urinary retention in men (e.g., previously diagnosed benign prostatic hypertrophy)
B. AP, defined as acute flank pain (onset within 7 days prior to randomization) or costovertebral angle (CVA) tenderness on physical examination, plus at least ONE of the following new-onset or worsening symptoms or signs:
-Fever (oral, tympanic, or rectal temperature more than 38°C [more than 100.4°F]), which must be observed and documented by a health care provider
-Nausea or vomiting
-Dysuria, increased urinary frequency, or urinary urgency Note: If criteria for both cUTI and AP are met, cUTI will be considered the study entry diagnosis for randomization and analysis purposes.
4. Evidence of pyuria within 48 hours prior to randomization, as determined by an adequate clean catch urine specimen for culture or other appropriate method to collect a urine culture that minimizes risk of bacterial contamination with ONE of the following findings:
-Positive leukocyte esterase on urinalysis, (where positive result is at least or moderate as indicated on a urine dipstick)
-WBC count more than and equal to 10 cells/mm3 in unspun urine
-WBC count more than and equal to 10 cells/ HPF in urine sediment (spun urine) Note: The screening/baseline urine sample (within 48 hours prior to randomization) will be submitted for culture; however, subjects may be randomized and administered study drug therapy prior to knowledge of screening/baseline urine culture results.
5. If known, the screening/baseline urine culture taken within 48 hours prior to randomization contains more than and equal to 105 CFU/mL of a Gram-negative uropathogen likely to be susceptible to meropenem
6. Expectation, in the judgment of the Investigator, that any implanted urinary instrumentation (e.g., nephrostomy tubes, ureteric stents) will be surgically removed or replaced before randomization or within 24 hours after randomization, unless removal or replacement is considered unsafe or contraindicated;
note that temporary urethral catheters that have been in place for more than 24 hours prior to Screening must be removed or replaced prior to collection of the Screening urine sample for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated
7. Requires hospitalization with administration of parenteral antibiotic therapy to manage the cUTI or AP in accordance with standard of care 8. All females must have a negative urine or serum pregnancy test (beta human chorionic gonadotropin [beta HCG]) at Screening AND agree to the use of one of the following highly effective methods of contraception from Screening through TOC:
-Surgical sterilization (defined as bilateral oophorectomy or bilateral salpingectomy, but excluding bilateral tubal occlusion)
-Post-menopausal (defined by amenorrhea for at least 24 months following cessation of all exogenous hormonal treatments)
-Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
-Progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
-Intrauterine device
-Intrauterine hormone releasing system
-Sexual intercourse with only vasectomized partners or
-Abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject
All males must agree to use an acceptable barrier method of birth control (i.e., condom) with female partner(s) and must not donate sperm from Screening through TOC
ExclusionCriteria
Details
1.Known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy, including but not limited to the following:
-Perinephric or renal abscess
-Uncomplicated lower UTI
-Recent trauma to the pelvis or urinary tract
-Polycystic kidney disease
-Chronic vesicoureteral reflux
-Previous or planned cystectomy or permanent urinary diversion (e.g., ileal loop, cutaneous ureterostomy)
-Acute or chronic bacterial prostatitis, orchitis, or epididymitis
-Concurrent non-renal source of infection (e.g., endocarditis, osteomyelitis, abscess, meningitis, pneumonia)
-Previous or planned renal transplant or subject requiring hemodialysis
-cUTI or AP that is known at Screening to be caused by a pathogen that is resistant to meropenem, including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis)
2.Receipt of potentially effective systemic antibacterial therapy within 72 hours prior to randomization, with the exception of any of the following:
-Receipt of a single dose of an allowed short acting antibacterial agent within 72 hours prior to randomization. For subjects without documentation of failure on this prior therapy and/or documented uropathogen resistant to this prior therapy, this exception will be capped at a maximum of 25 percent of enrollment.
-Receipt of more than 48 hours of prior antibiotic therapy and in the Investigators opinion, failed that prior antibiotic therapy
-Documented to have cUTI or AP caused by a pathogen that is not susceptible to the prior antibiotic therapy
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
4. Pregnant or breastfeeding women
5. Likely to require more than 10 days of antibiotic treatment to cure the current acute cUTI, or likely to receive any additional systemic antimicrobial therapy during the study period (including antibacterial, antimycobacterial, or antifungal therapy or prophylaxis) other than study drug, with the exception of (1) a single oral dose of any antifungal treatment for vaginal candidiasis, or (2) a glycopeptide (e.g., vancomycin), oxazolidinone (e.g., linezolid), or daptomycin given for a Gram-positive infection 6. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy)
7. History of epilepsy or known seizure disorder requiring current treatment with anti-seizure medication
8. Creatinine clearance less than 30 mL/min or requirement for hemodialysis or CVVH
9. Current or anticipated neutropenia defined as less than 500 neutrophils/mm3 , or platelet count less than 50,000 per microliter
10. Screening serum total bilirubin more than and equal to 2 times the ULN (unless elevated indirect bilirubin due to known Gilberts syndrome), or AST or ALT more than and equal to 5 times ULN, or alkaline phosphatase more than and equal to 2 times ULN
11. History of Clostridioides difficile associated disease within 6 months prior to enrolment 12. History of serious or significant hypersensitivity or allergic reaction (e.g., anaphylaxis, urticaria, other significant reaction) to any β lactam antibiotic or the excipient L arginine
13. Prior receipt of FEP TAZ, prior randomization in this study, or use of any experimental drug or device within 30 days prior to enrolment
14. Unlikely to comply with the protocol (e.g., inability to return for all study visits), or any condition or clinically significant abnormality that, in the opinion of the Investigator, is likely to interfere with optimal study participation (e.g., evaluation of study drug efficacy, determination of safety, or completion of the expected course of treatment)
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
To assess the overall safety and tolerability of FEP-TAZ in the Safety
population
Test of Cure visit - Day 28
Secondary Outcome
Outcome
TimePoints
ï‚· To assess the clinical outcome at EOT (MITT and mMITT populations) and
at TOC (mMITT and CE populations)
ï‚· To assess the microbiological outcome at EOT (mMITT population) and at
TOC (mMITT and ME populations)
ï‚· To assess the by-pathogen clinical (mMITT and CE populations) and
microbiological outcomes (mMITT and ME populations) at TOC
Randomization/Day 1: Day 1 is calendar day of first dose of study drug
ï‚· Day 1 through Day 10: Treatment period. All subjects will receive 7 to 10
days of study drug
ï‚· EOT: Last day of study drug administration (FEP-TAZ or meropenem),
or within 24 hours after completion of the last infusion of study drug
 TOC: Day 17 ± 2 days, inclusive
 LFU: Day 26 ± 4 days. The LFU assessments may be conducted via
telephone contact or by another interactive technology
Target Sample Size
Total Sample Size="304" Sample Size from India="304" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Wockhardt is developing FEP-TAZ (also known as WCK 4282), which is a combination of cefepime
hydrochloride (FEP, an available 4th-generation cephalosporin) and tazobactam (TAZ, a clinically wellestablished inhibitor of certain Class A and Class C β-lactamases). FEP was first approved for clinical use in
1996, and since then has been approved for multiple indications (e.g., cUTI, complicated intra-abdominal
infection, neutropenic fever, pneumonia). TAZ has been combined with piperacillin and more recently with
a newer cephalosporin, ceftolozane. FEP-TAZ is a sterile powder blend of FEP hydrochloride (2 g) and TAZ
sodium (2 g) for administration as an IV infusion.
Combination Product Name: FEP-TAZ [cefepime hydrochloride + tazobactam sodium] for Injection
Chemical name of FEP component: 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8-
oxo-5-thia-1-azabicyclo[4.2.0] oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride,72-(Z)-(Omethyloxime), monohydrochloride, monohydrate.
Chemical name of TAZ component: Sodium (2S, 3S, 5R)-3-methyl-7-oxo-3-(1H-1, 2, 3-triazol-1-ylmethyl)-
4-thia- 1-azabicyclo [3.2.0] heptane-2-carboxylate-4,4-dioxide.
In vitro and in vivo microbiologic studies indicate that FEP-TAZ has potent activity against ESBL- and Class
C β-lactamase-producing Gram-negative pathogens. Against a large number of Gram-negative isolates
collected worldwide in 2014, the minimum inhibitory concentration of FEP-TAZ to inhibit 90% (MIC90) of
MDR pathogens ― including strains producing both Class A + C β-lactamases ― were significantly lower
than ceftolozane-tazobactam MIC90 values and comparable to meropenem and ceftazidime-avibactam
MIC90s (Sader, 2017)15. The spectrum of activity of FEP-TAZ is similar to that of carbapenems and
encompasses most clinically-important MDR Gram-negative pathogens (e.g., Enterobacterales and P.
aeruginosa that produce ESBLs, AmpC, and selected Class A and Class D carbapenemases, such as KPC and
OXA-181), with the exception of metallo-β-lactamase-producing pathogens and MDR Acinetobacter spp.
TAZ also restores the activity of FEP against anaerobic pathogens, such as Bacteroides spp. and
Fusobacterium spp. Owing to the potent activity of FEP against susceptible Gram-positive pathogens (e.g.,
methicillin-sensitive S. aureus, Streptococcus pneumoniae, S. pyogenes and E. faecalis, FEP-TAZ ― unlike
ceftazidime-avibactam or ceftolozane-tazobactam ― is likely to provide a monotherapy option for serious
polymicrobial infections involving susceptible Gram-negative, Gram-positive aerobic pathogens, and
anaerobic pathogens.