Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis

NCT05887908 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: OP0595-5
• Study Type: interventional
• Target: 614
• Locations: 9 countries
• Sites: 61

Brief Summary

Phase 3 study to evaluate the efficacy and safety of cefepime/nacubactam or aztreonam/nacubactam compared to imipenem/cilastatin in the treatment of complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AP).

Conditions

cUTI; AP; Complicated Urinary Tract Infection; Acute Pyelonephritis

Keywords

OP0595; nacubactam; Integral

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Achieve Composite Clinical and Microbiological Success at TOC (Test of Cure Visit) in the Microbiological Modified Intent-to-Treat (m-MITT) Population

  Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.

  TOC (Test of Cure visit): 7 [±2] days after EOT (end of treatment) [Day 10 to 23 after the start of treatment]

Secondary Outcomes (7)

• Proportion of Patients Who Achieve Composite Clinical and Microbiological Outcome

  Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

• Proportion of Patients With a Clinical Outcome of Cure

  Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

• Proportion of Patients With a Microbiological Outcome of Eradication

  Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30

• Proportion of Patients With a Clinical Outcome of Cure at TOC in Patients With Secondary Bacteremia at Baseline

  TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment

• Proportion of Patients With a Microbiological Outcome of Eradication at TOC in Patients With Secondary Bacteremia at Baseline

  TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment

Study Arms (3)

co-administration of cefepime and nacubactam

EXPERIMENTAL

co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)

Drug: co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam

EXPERIMENTAL

co-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)

Drug: co-administration of aztreonam and nacubactam

imipenem/cilastatin

ACTIVE COMPARATOR

combination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)

Drug: imipenem/cilastatin

Interventions

imipenem/cilastatin DRUG

1 g imipenem/1 g cilastatin

imipenem/cilastatin

co-administration of cefepime and nacubactam DRUG

2 g cefepime and 1 g nacubactam

co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam DRUG

2 g aztreonama and 1 g nacubactam

co-administration of aztreonam and nacubactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients at least18 years of age (or age of legal consent, whichever is older) at the time of obtaining informed consent and who can be hospitalized throughout the Treatment Period;
• Weight at most 140 kg;
• Expectation, in the opinion of the Investigator, that the patient's cUTI or AP will require treatment with at least 5 days of IV antibiotics;

You may not qualify if:

• Has a known imipenem- and/or meropenem-resistant Gram-negative uropathogen (at least 10\^5 CFU/mL), isolated from study-qualifying urine culture; Note: If after randomization the susceptibility testing indicates resistance to imipenem and/or meropenem, the patient may remain on the study drug at the Investigator's discretion.
• Has known or suspected single or concurrent infection with Acinetobacter spp. or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and needs to be managed with other anti-infectives; Note: Patients with qualifying pathogen coinfected with a Gram-positive pathogen may be administered narrow spectrum, open-label glycopeptide (eg, vancomycin), oxazolidinone (eg, linezolid), or daptomycin concomitantly with the study drug at the Investigator's discretion.
• Has only a known Gram-positive primary uropathogen (at least 10\^5 CFU/mL), isolated from study qualifying urine culture;

Sponsors & Collaborators

• Meiji Seika Pharma Co., Ltd.: lead

Study Sites (61)

Meiji Research Site

Pleven, Bulgaria

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Meiji Research Site

Rousse, Bulgaria

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Meiji Research Site

Silistra, Bulgaria

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Meiji Research Site

Sofia, Bulgaria

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Meiji Research Site

Beijing, China

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Meiji Research Site

Changchun, China

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Meiji Research Site

Chongqing, China

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Meiji Research Site

Fuyang, China

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Meiji Research Site

Ganzhou, China

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Meiji Research Site

Huaian, China

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Meiji Research Site

Huzhou, China

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Meiji Research Site

Nanchang, China

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Meiji Research Site

Nanning, China

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Meiji Research Site

Quanzhou, China

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Meiji Research Site

Shanghai, China

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Meiji Research Site

Shantou, China

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Meiji Research Site

Shijiazhuang, China

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Meiji Research Site

Taian, China

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Meiji Research Site

Tianjin, China

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Meiji Research Site

Xuancheng, China

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Meiji Research Site

Yunnan, China

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Zhejiang, China

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Meiji Research Site

Zhengzhou, China

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Meiji Research Site

Hradec Králové, Czechia

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Meiji Research Site

Liberec, Czechia

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Meiji Research Site

Prague, Czechia

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Meiji Research Site

Ústí nad Labem, Czechia

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Meiji Research Site

Meegomäe, Võrumaa, Estonia

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Meiji Research Site

Kohtla-Järve, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Meiji Research Site

Kutaisi, Georgia

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Rustavi, Georgia

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Meiji Research Site

Tbilisi, Georgia

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Meiji Research Site

Fukuyama, Japan

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Meiji Research Site

Gifu, Japan

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Meiji Research Site

Ibaraki-Town, Higashiibaraki-County, Japan

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Meiji Research Site

Iwakuni, Japan

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Meiji Research Site

Kanazawa, Japan

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Meiji Research Site

Kawachi-Nagano, Japan

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Meiji Research Site

Kofu, Japan

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Meiji Research Site

Kumamoto, Japan

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Meiji Research Site

Matsumoto, Japan

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Meiji Research Site

Mizumaki-Town, Onga-County, Japan

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Meiji Research Site

Nagasaki, Japan

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Meiji Research Site

Nankoku, Japan

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Meiji Research Site

Ōita, Japan

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Meiji Research Site

Ōtake, Japan

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Meiji Research Site

Sagamihara, Japan

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Meiji Research Site

Sapporo, Japan

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Meiji Research Site

Shinjuku-ku, Japan

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Meiji Research Site

Toyota, Japan

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Meiji Research Site

Ueda, Japan

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Meiji Research Site

Yokohama, Japan

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Meiji Research Site

Riga, Latvia

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Meiji Research Site

Valmiera, Latvia

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Meiji Research Site

Kaunas, Lithuania

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Meiji Research Site

Vilnius, Lithuania

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Meiji Research Site

Galanta, Slovakia

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Meiji Research Site

Rimavská Sobota, Slovakia

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Meiji Research Site

Svidník, Slovakia

Location

MeSH Terms

Interventions

nacubactam; Cilastatin, Imipenem Drug Combination

Intervention Hierarchy (Ancestors)

Imipenem; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Cilastatin; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

The analysis plan included subgroup analyses by pathogen for some secondary endpoints. However, there were a large number of pathogen types, most of which were rare and sparsely represented in the dataset. Therefore, we present the results of subgroup analyses for only the two most frequent pathogens, as analyses for the others were considered statistically unreliable and clinically uninformative.

Results Point of Contact

• Title: Meiji Seika Pharma Clinical Trial Administrator
• Organization: Clinical Development Department

clinical-trials@meiji.com

(+81) 3-3273-3745

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2023
• First Posted: June 5, 2023
• Study Start: May 23, 2023
• Primary Completion: November 22, 2024
• Study Completion: November 26, 2024
• Last Updated: December 24, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Locations

CN (19); LA (2); JP (20); LI (2); SL (3); CZ (4); GE (3); ES (4); BU (4)