Xeruborbactam + Cefiderocol for Bacterial Infections

Recruiting at 1 trial location

Overseen By Jeff Loutit, MBChB

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Qpex Biopharma, Inc.

Must not be taking: Beta-lactams

Disqualifiers: Cardiovascular, Pulmonary, Renal, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase 1, randomized, double blind, placebo controlled drug-drug interaction, pharmacokinetics and safety study of cefiderocol in combination with xeruborbactam in healthy adult participants

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Xeruborbactam/Cefiderocol for bacterial infections?

Cefiderocol, a component of the drug, has shown effectiveness in treating serious Gram-negative bacterial infections, including complicated urinary tract infections and pneumonia, by overcoming many bacterial resistance mechanisms. However, some studies noted higher mortality rates in patients treated with cefiderocol, indicating the need for careful consideration in its use. ^{1 2 3 4 5}

Is the combination of Xeruborbactam and Cefiderocol safe for humans?

Cefiderocol, also known as Fetroja, has been studied in clinical trials and generally showed a good safety profile, but some studies reported higher mortality rates in patients with severe infections. Common side effects include stomach issues like diarrhea and nausea. ^{1 2 3 5 6}

What makes the drug Xeruborbactam/Cefiderocol unique for bacterial infections?

Xeruborbactam/Cefiderocol is unique because it combines cefiderocol, a novel siderophore cephalosporin that uses iron transport channels to penetrate Gram-negative bacteria, with xeruborbactam, potentially enhancing its effectiveness against multidrug-resistant strains. This combination targets serious Gram-negative bacterial infections, offering a new option for patients with limited treatment choices. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for healthy adults who can participate in a study to understand how two drugs interact with each other. Specific eligibility details are not provided, but typically participants should have no significant health issues.

Inclusion Criteria

Body mass index (BMI) ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg

I am in good health as confirmed by recent medical exams.

Voluntary consent to participate in the study

Exclusion Criteria

Documented hypersensitivity reaction or anaphylaxis to any medication

I am allergic to certain antibiotics like penicillins or cephalosporins.

I have no major health issues apart from my current condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single fixed dose of Xeruborbactam, Cefiderocol, or a combination of both, or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and pharmacokinetic parameters after dosing

17 days

Multiple visits (in-person)

Treatment Details

Interventions

• Xeruborbactam/Cefiderocol

Trial Overview The study tests the interaction between Xeruborbactam and Cefiderocol, both antibiotics, in healthy adults. It's randomized and placebo-controlled, meaning some people get the real drugs while others get an inactive substance without knowing which one they received.

Participant Groups

Group I: Single Dose Cohorts Experimental Treatment 3 Interventions

Administered single fixed dose of Xeruborbactam Administered single fixed dose of Cefiderocol Administered single fixed dose of a combination of Xeruborbactam and Cefiderocol.

Group II: Single Dose Cohorts Placebo Placebo Group 1 Intervention

5% Dextrose in water

Xeruborbactam/Cefiderocol is already approved in United States for the following indications:

Approved in United States as Fetroja (cefiderocol) for:

• Complicated urinary tract infections including pyelonephritis
• Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia

Who Is Running the Clinical Trial?

Qpex Biopharma, Inc.

Lead Sponsor

Trials

8

Recruited

460+

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Shionogi Inc.

Industry Sponsor

Trials

10

Recruited

760+

Findings from Research

Cefiderocol is the first siderophore cephalosporin approved for treating serious Gram-negative bacterial infections, showing strong effectiveness against multidrug-resistant strains and stability against various β-lactamases.

In clinical trials, cefiderocol was found to be noninferior to standard treatments for complicated urinary tract infections and nosocomial pneumonia, although it had a higher all-cause mortality rate in patients with carbapenem-resistant infections, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections. Syed, YY.[2023]

Cefiderocol is a new antibiotic that effectively targets Gram-negative bacteria by utilizing their iron transport systems, making it a promising option for treating complicated urinary tract infections and certain types of pneumonia in adults with limited treatment options.

However, the CREDIBLE-CR trial indicated a higher all-cause mortality in patients treated with cefiderocol, particularly those with severe infections from Acinetobacter spp., highlighting the need for further phase III studies to assess its safety and efficacy in serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria. Silva, JT., López-Medrano, F.[2023]

Cefiderocol is a new antibiotic effective against difficult-to-treat gram-negative bacteria, including those resistant to carbapenems, as shown in clinical trials for hospital-acquired pneumonia.

Despite its efficacy, a clinical trial indicated an increase in mortality in patients treated with cefiderocol, highlighting the need for further evaluation of its safety and effectiveness in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol. Soriano, MC., Montufar, J., Blandino-Ortiz, A.[2023]

Cefiderocol is a newly approved antibiotic that shows effectiveness against multidrug-resistant (MDR) bacteria, including common pathogens in cystic fibrosis patients, such as Pseudomonas aeruginosa and Stenotrophomonas maltophilia.

While cefiderocol has demonstrated potential with minimum inhibitory concentrations (MICs) of ≤4 mg/L, there is currently no in vivo evidence specifically in cystic fibrosis patients, suggesting it should be considered when other treatment options are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Cefiderocol Have a Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management? Gavioli, EM., Guardado, N., Haniff, F., et al.[2023]

Cefiderocol is effective against complicated urinary tract infections (cUTIs) caused by Gram-negative bacteria, showing a higher clinical and microbiological eradication rate compared to imipenem-cilastatin (73% vs. 55%).

Despite its efficacy, cefiderocol is associated with higher all-cause mortality in certain patients, and its use should be restricted to cases where alternative treatments are limited, particularly in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-Resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety. Lee, YR., Yeo, S.[2023]

Cefiderocol is a novel antibiotic that effectively targets multi-drug resistant (MDR) Gram-negative bacteria by utilizing a unique mechanism that allows it to transport iron across bacterial membranes, leading to cell wall synthesis inhibition.

While cefiderocol showed non-inferiority to other antibiotics like imipenem and meropenem in treating complicated urinary tract infections and hospital-acquired pneumonia, it was associated with higher all-cause mortality in patients with severe infections from Acinetobacter spp., highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol: a novel siderophore cephalosporin for multidrug-resistant Gram-negative bacterial infections. Parsels, KA., Mastro, KA., Steele, JM., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Cefiderocol. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Does Cefiderocol Have a Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management? [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-Resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Cefiderocol: a novel siderophore cephalosporin for multidrug-resistant Gram-negative bacterial infections. [2023]