Complicated urinary tract infection (cUTI) and acute uncomplicated pyelonephritis (AP) MedDRA version: 21.0 Level: LLT Classification code 10080628 Term: Complicated urinary tract infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: LLT Classification code 10001032 Term: Acute pyelonephritis System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Meiji Seika Pharma Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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; Complete list of inclusion criteria is in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 360 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 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; Complete list of exclusion criteria is in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: The secondary objectives of this study are the following: • To assess the efficacy of aztreonam/nacubactam administered by IV infusion in patients with cUTI or AP; • To assess the efficacy of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion in patients with secondary bacteremia due to cUTI or AP; • To assess the pharmacokinetics (PK) of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion in patients with cUTI or AP; and • 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. ;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: 1. At the assessment of Clinical Signs and Symptoms 2. At the assessment of clinical outcome 3. At the assessment of Microbiological Outcome: - urine culture: Urine samples will be obtained at Screening, prior to the first dose of study drug on Day 1, EA (Early Assessment), EOT, TOC, FUP (if clinically indicated), and ET (Early Termination). - blood culture: Two sets of blood culture samples from 2 separate venipuncture sites will be obtained at Screening and prior to the first dose of study drug on Day 1 for baseline blood cultures. 4. At the assessment of Composite Clinical and Microbiological Succe | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints for cUTI and AP include the following: • The proportion of patients with composite clinical and microbiological success at TOC in the Clinically Evaluable (CE) and Microbiologically Evaluable (ME) Populations; • The proportion of patients with composite clinical and microbiological success at EA, EOT, and FUP in the m MITT Population; • 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; • 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; • 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 • 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. Secondary Efficacy Endpoints for Secondary Bacteremia: Patients with cUTI who meet the following conditions will be determined programmatically as secondary bacteremia: • Isolation of a Gram-negative bacteria from at least 1 blood culture at baseline AND this isolated pathogen is also identified from the site of infection; AND • At least 1 of the following within 24 hours prior to the first dose of study drug: a. Fever (oral or tympanic temperature = 38°C [= 100.4°F] or rectal/core temperature =38.3°C [= 100.9°F]) OR hypothermia (rectal/core temperature 10,000/mm3); c.> 15% immature polymorphonuclear neutrophils (bands) regardless of peripheral WBC count; d. Leukopenia (WBC 100 bpm; f. Tachypnea > 20 breaths/min; g. Hypotension, systolic 20 mg/dL. Clinical | — |
Countries
Bulgaria, China, Czechia, Czech Republic, Estonia, Georgia, Japan, Latvia, Lithuania, Slovakia
Contacts
Public ContactClinical Trial Management
Medpace, Inc.
Outcome results
None listed