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

Sponsor

Wockhardt (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04979806

Collaborator

Medpace, Inc. (Industry)

528

Enrollment

Locations

Arms

12.1

Anticipated Duration (Months)

11.5

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Complicated Urinary Tract Infection Acute Pyelonephritis	Drug: Cefepime-zidebactam (FEP-ZID) Drug: Meropenem	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

528 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 28, 2022

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cefepime-zidebactam (FEP-ZID)	Drug: Cefepime-zidebactam (FEP-ZID) 3 g (2 g FEP + 1 g ZID) IV q8h
Active Comparator: Meropenem	Drug: Meropenem 1 g IV q8h

Arm

Intervention/Treatment

Experimental: Cefepime-zidebactam (FEP-ZID)

Drug: Cefepime-zidebactam (FEP-ZID)

3 g (2 g FEP + 1 g ZID) IV q8h

Active Comparator: Meropenem

Drug: Meropenem

1 g IV q8h

Outcome Measures

Primary Outcome Measures

Percentage of subjects with overall success at Test-of-Cure [Test Of Cure Visit (Day 17 ± 2 days)]
Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) 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)
Percentage of subjects with Treatment-Emergent Adverse Events (TEAE) [Day 1 to the end of study Late Follow-Up visit (LFU) (26 ± 2 days)]]
Collection of number of adverse events.

Secondary Outcome Measures

Percentage of subjects with overall success at End-of-Treatment [End of Treatment Visit (Day 7 - 10 ± 1 day)]
Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (<1000 CFU/mL)
Percentage of subjects with clinical cure at End-of-Treatment [End of Treatment Visit (Day 7 - 10 ± 1 day)]
Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL)(CFU)/mL.
Percent of subjects with microbiological eradication at End-of-Treatment [End of Treatment Visit (Day 7 - 10 ± 1 day)]
Microbiologic eradication is defined as demonstrating <1000 CFU/mL of the bacterial pathogen found at study entry
Percentage of subjects with clinical cure at Test-of-Cure [End of Treatment Visit (Day 17 ± 2 days)]
Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL)
Percent of subjects with microbiological eradication at Test-of-Cure [End of Treatment Visit (Day 17 ± 2 days)]
Microbiologic eradication is defined as demonstrating <1000 CFU/mL of the bacterial
Percentage of subjects with clinical cure at Late Follow-up [End of Treatment Visit (Day 26 ± 2 days)]
Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL)
Plasma Concentration of FEP-ZID [On Days 1 and 3 of dosing prior to infusion, within 15 minutes after the end of infusion, and at 3 timepoints up to 7 hours hours post infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female ≥ 18 years of age
Provide a signed written informed consent prior to any study-specific procedures
Meet the clinical criteria for either cUTI or AP
Requires hospitalization to manage the cUTI or AP
Agrees to use effective methods of contraception

Exclusion Criteria:

Known or suspected disease that may confound the assessment of efficacy.
Receipt of more than 72 hours of prior antibiotic therapy except for those failing prior antibiotic therapy and/or having documented uropathogen resistant to the prior therapy.
Rapidly progressive illness such that the subject is unlikely to survive the study period.
Pregnant or breastfeeding women
History of a seizure disorder requiring current treatment
Creatinine clearance < 15 mL/min or on renal dialysis
Neutropenia or elevated liver enzymes
Hypersensitivity to beta-lactam antibiotics
Unlikely to comply with the protocol or the Investigator considers that study participation may not be optimal for the subject

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chula Vista	Chula Vista	California	United States	91911
2	St. Louis	Saint Louis	Missouri	United States	63110
3	Brest	Brest		Belarus	224027
4	Gomel	Gomel		Belarus	246029
5	Grodno	Grodno		Belarus	230027
6	Grodno	Grodno		Belarus	230030
7	Minsk	Minsk		Belarus	220036
8	Minsk	Minsk		Belarus	220045
9	Minsk	Minsk		Belarus	223041
10	Vitebsk	Vitebsk		Belarus	210037
11	Pleven	Pleven		Bulgaria	5800
12	UMHAT Dr. Georgi Stranski	Pleven		Bulgaria
13	Plovdiv	Plovdiv		Bulgaria	4003
14	Sofia	Sofia		Bulgaria	1407
15	Sofia	Sofia		Bulgaria	1431
16	Changsha	Changsha		China	410005
17	Changsha	Changsha		China	410011
18	Changsha	Changsha		China	410018
19	Chengdu	Chengdu		China	610041
20	Chongqing	Chongqing		China	400010
21	Liaoyang	Liaoyang		China	110016
22	Shanghai	Shanghai		China	200040
23	Ahmedabad	Ahmedabad	Gujarat	India	380052
24	Sūrat	Sūrat	Gujarat	India	395002
25	Hisar	Hisar	Haryana	India	125001
26	Bengaluru	Bengaluru	Karnataka	India	560001
27	Nagpur	Nagpur	Maharashtra	India	440003
28	Chandigarh	Chandigarh	Punjab	India	160012
29	Kolkata	Kolkata	West Bengal	India	700020
30	Kaunas	Kaunas		Lithuania	50009
31	Klaipeda	Klaipeda		Lithuania	LT-92288
32	Vilnius	Vilnius		Lithuania	08661
33	Vilnius	Vilnius		Lithuania	LT-04130
34	Vilnius	Vilnius		Lithuania	LT-10207
35	Chihuahua	Chihuahua		Mexico	31238
36	Cuernavaca	Cuernavaca		Mexico	62290
37	Guadalajara	Guadalajara		Mexico	44280
38	Mérida	Mérida		Mexico	C.P 97000
39	San Luis Potosí	San Luis Potosí		Mexico	78290
40	Cusco	Cusco		Peru	08000
41	Iquitos	Iquitos		Peru	16001
42	Lima	Lima		Peru	15072
43	Lima	Lima		Peru	15082
44	Krakow	Krakow		Poland	31-559
45	Lodz	Lodz		Poland	90-153
46	Ostroleka	Ostroleka		Poland	07-410