Study to Assess the Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in the Treatment of Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis, in Adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Meiji Seika Pharma Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

18 May 2023 → 27 Nov 2024

Decision date (initial)

2024-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Japan Agency for Medical Research and Development

External identifiers

EU CT number

2024-515463-55-00

EudraCT number

2021-001441-12

WHO UTN

U1111-1309-2995

ClinicalTrials.gov

NCT05887908

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy

The primary objective of this study is to assess the efficacy and safety of cefepime/nacubactam and to assess the safety of aztreonam/nacubactam administered by intravenous (IV) infusion compared to imipenem/cilastatin in patients with cUTI or AP.

Secondary objectives 4

1. To assess the efficacy of aztreonam/nacubactam administered by IV infusion in patients with cUTI or AP;
2. To assess the efficacy of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion in patients with secondary bacteremia due to cUTI or AP;
3. To assess the pharmacokinetics (PK) of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion in patients with cUTI or AP; and
4. To assess clinical and microbiological response of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion per type of pathogen, type of resistance, and antimicrobial susceptibility.

Conditions and MedDRA coding

Complicated urinary tract infection (cUTI) and acute uncomplicated pyelonephritis (AP)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male or female patients ≥ 18 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;
2. Weight ≤ 140 kg
3. 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;
4. Note: Complete list of inclusion criteria is in the protocol.

Exclusion criteria 4

1. Has a known imipenem- and/or meropenem-resistant Gram-negative uropathogen (≥ 105 CFU/mL), isolated from study-qualifying urine culture;
2. Has known or suspected single or concurrent infection with Acinetobacter species 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;
3. Has only a known Gram-positive primary uropathogen (≥ 105 CFU/mL), isolated from study qualifying urine culture;
4. Note: Complete list of exclusion criteria is in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the 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.

Secondary endpoints 15

1. The secondary efficacy endpoints for cUTI and AP include the following:
2. The proportion of patients with composite clinical and microbiological success at TOC in the Clinically Evaluable (CE) and Microbiologically Evaluable (ME) Populations;
3. The proportion of patients with composite clinical and microbiological success at EA, EOT, and FUP in the m MITT Population;
4. The proportion of patients with a microbiological outcome of eradication at EA, EOT, TOC, and FUP in the m MITT Population and at TOC in the ME Population;
5. The proportion of patients with a clinical outcome of cure at EA, EOT, TOC, and FUP in the m MITT Population and at TOC in the CE and ME Populations;
6. The proportion of patients with a clinical outcome of cure at EA, EOT, TOC, and FUP in the m-MITT Population and at TOC in the CE and ME Populations and microbiological outcome of eradication at EA, EOT, TOC, and FUP in the m-MITT Population and at TOC in the ME Population per type of pathogen, type of resistance, and antimicrobial susceptibility; and
7. The proportion of patients with composite clinical outcome of recurrence and/or microbiological outcome of recurrence at the FUP in the m-MITT, CE, and ME population.
8. The secondary efficacy endpoints for secondary bacteremia include the following:
9. The proportion of patients with composite clinical and microbiological success of cUTI or AP at TOC in the m-MITT, CE, and ME Populations;
10. The proportion of patients with a clinical outcome of cure from cUTI or AP at TOC in the m-MITT, CE, and ME Populations;
11. The proportion of patients with a microbiological outcome of eradication from cUTI or AP at TOC in the m-MITT and ME Populations;
12. The proportion of patients with a clinical outcome of cure from secondary bacteremia at TOC in the m-MITT, CE, and ME Populations;
13. The proportion of patients with a microbiological outcome of eradication from secondary bacteremia at TOC in the m-MITT and ME Populations;
14. The proportion of patients in the m-MITT and ME Populations free from the definition of secondary bacteremia AND a clinical outcome of cure from cUTI or AP AND a microbiological outcome of eradication from cUTI or AP at TOC; and
15. The proportion of patients who are free from secondary bacteremia at TOC in the m-MITT and ME Populations.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Meiji Seika Pharma Co. Ltd.

Sponsor organisation

Meiji Seika Pharma Co. Ltd.

Address

4-16 Kyobashi 2-chome Chuo-ku

City

Chuo

Postcode

104-8002

Country

Japan

Scientific contact point

Organisation

Meiji Seika Pharma Co. Ltd.

Contact name

Regulatory Submissions

Public contact point

Organisation

Meiji Seika Pharma Co. Ltd.

Contact name

Regulatory Submissions

Third parties 5

Locations

6 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications