Xeruborbactam + Ceftibuten for Bacterial Infection

No longer recruiting at 1 trial location

Overseen By Shawnee Gehrke, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Qpex Biopharma, Inc.

Must not be taking: Antibiotics, Antacids, H2 blockers, PPIs

Disqualifiers: Unstable medical conditions, Seizures, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, ceftibuten and xeruborbactam (an oral prodrug), to assess safety and behavior in the body, particularly for individuals with kidney issues. The goal is to understand how this treatment works in those with varying degrees of kidney function, from mild to severe impairment, and compare it with those who have normal kidney function. Participants should have kidney problems that affect daily life but are not on dialysis, or be healthy individuals with normal kidney function for comparison. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use medications that affect the elimination of serum creatinine or compete with renal tubular secretion within 30 days before the trial or during it. Also, certain over-the-counter and prescription drugs, like antacids, are prohibited 7 days before the trial starts.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using ceftibuten and xeruborbactam together can cause side effects like diarrhea and minor changes in liver function, which usually resolve quickly after stopping the treatment. Other studies have found that about 60% to 70% of ceftibuten is excreted unchanged in urine, indicating efficient processing by the body. This combination is currently being tested in early studies to assess its safety for people. Early studies primarily focus on evaluating the safety of a treatment for the first time, so further research is needed to understand all possible effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Xeruborbactam and Ceftibuten because it introduces a fresh approach to tackling bacterial infections, especially in patients with varying kidney function. Unlike traditional antibiotics, Xeruborbactam acts as a beta-lactamase inhibitor, which means it helps Ceftibuten work more effectively against bacteria that have become resistant to other treatments. This combination could offer a powerful option for patients with resistant infections, providing a potential new line of defense. Additionally, the oral administration of this combination could make it more convenient and accessible compared to some intravenous antibiotics.

What evidence suggests that this trial's treatments could be effective for bacterial infection?

Research has shown that ceftibuten effectively treats respiratory and complicated urinary tract infections, performing as well as ongoing intravenous treatments. Xeruborbactam, a new drug, inhibits certain enzymes called β-lactamases, which enable bacteria to resist antibiotics. Lab studies demonstrated that xeruborbactam reduced bacterial resistance to other antibiotics, enhancing their effectiveness. In this trial, participants will receive a combination of ceftibuten and xeruborbactam. Although no human data yet exists for using ceftibuten and xeruborbactam together, xeruborbactam's mechanism suggests it could enhance ceftibuten's effectiveness against difficult infections. ^{1 3 5 6 7}

Who Is on the Research Team?

Jeff Loutit, MBChB

Principal Investigator

Qpex Biopharma, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with renal impairment (eGFR < 90 mL/min) who can sign consent and follow the study protocol. Men must use contraception or abstain from sex, while women need to be postmenopausal, surgically sterile, or using birth control. Participants should have a stable pulse rate and not consume alcohol before dosing.

Inclusion Criteria

I am a woman who cannot have children, either due to menopause or sterilization.

Your heart rate while sitting is between 45 and 110 beats per minute.

I understand the study requirements and am willing to follow them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of ceftibuten and xeruborbactam oral prodrug

1 day

1 visit (in-person)

Observation

Participants remain in the clinic for post-dose procedures

7 days

In-clinic stay

Follow-up

Participants are contacted by phone for follow-up

2-4 days

Phone contact

What Are the Treatments Tested in This Trial?

Interventions

• Ceftibuten
• Xeruborbactam Oral Prodrug

Trial Overview The study tests the safety and how the body processes ORAvance, a combination of ceftibuten/xeruborbactam oral prodrug (QPX7831), in those with kidney issues. It's an open-label Phase 1 trial where everyone gets a single dose of the drug to see how it works.

How Is the Trial Designed?

Group I: Open Label, Single Dose Combination of Ceftibuten & Xeruborbactam oral prodrug Experimental Treatment 2 Interventions

24 pts will be enrolled with varying degrees of RI as well as 8 participants with normal renal function (NRF). 8 participants will be enrolled in each group (G) based on estimated glomerular function rate (eGFR) at screening: * G1: Mild RI (eGFR 60 to 90 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation \[CKP-EPI\]) adjusted for the participant's body surface \[BSA\]) * G2: Moderate RI (eGFR 30 to \< 60 mL/min/1.73m2 calculated using the CKD-EPI equation adjusted for the participant's BSA) * G3: Severe RI (eGFR \< 30 mL/min/1.73m2 calculated using the CKD-EPI equation) not receiving dialysis therapy * G4: Healthy participants with NRF matched to patients in Groups 1, 2 and 3 based on age, gender and BMI All pts will receive a single dose of ceftibuten \& QPX7831 on Day 1. Pts will remain in the clinic until completion of the post-dose procedures on Day 8. Participants will be contacted by phone between Days 10-12 for follow-up.

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+

Published Research Related to This Trial

In a study of 131 patients with respiratory and complicated urinary tract infections, oral ceftibuten was found to be as effective as continued parenteral therapy, with 67 out of 72 patients in the oral group achieving clinical cure.

Ceftibuten not only demonstrated similar efficacy but also reduced treatment costs by 44.3% compared to parenteral therapy, and no significant adverse effects were linked to its use, highlighting its safety as a step-down treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of ceftibuten++ in the sequential therapy of respiratory and urinary tract infections]. Székely, E., Ludwig, E.[2018]

Ceftibuten is the most effective oral cephalosporin against Enterobacteriaceae that produce plasmid-encoded broad spectrum beta-lactamases, outperforming several other antibiotics.

In a pharmacodynamic model, ceftibuten demonstrated bactericidal activity against Haemophilus influenzae and Streptococcus pneumoniae at concentrations similar to those achieved in human serum after a 200 mg oral dose taken twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases. Bauernfeind, A.[2019]

Ceftibuten is an effective oral antibiotic for treating various infections, including urinary tract infections and respiratory tract infections, showing similar or superior efficacy compared to other antibiotics like cefaclor and cotrimoxazole in clinical studies involving adults and children.

It has a good safety profile, with mild to moderate gastrointestinal side effects occurring in only 5 to 10% of patients, making it a promising alternative for infections caused by bacteria, especially those producing beta-lactamases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Wiseman, LR., Balfour, JA.[2018]

In a study of 62 patients with complicated urinary tract infections, both ceftibuten and cefixime were found to have similar clinical efficacy rates (78.3% for ceftibuten vs 77.3% for cefixime) and bacteriological eradication rates, indicating that both antibiotics are effective treatment options.

The safety profiles of ceftibuten and cefixime were comparable, with mild adverse effects reported in both groups, all of which resolved after treatment, suggesting that both medications can be safely administered without significant risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of ceftibuten and cefixime in the treatment of complicated urinary tract infections. Ho, MW., Wang, FD., Fung, CP., et al.[2018]

Ceftibuten combined with avibactam showed strong in vitro activity against various resistant Enterobacterales strains, inhibiting 90% of ESBL, KPC, and other β-lactamase producing isolates at low concentrations, indicating its potential effectiveness for treating complicated urinary tract infections.

This combination was found to be significantly more potent than ceftibuten alone and more effective than ceftazidime-avibactam against certain resistant strains, supporting the continued development of ceftibuten-avibactam as a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Activity of Ceftibuten-Avibactam against &#946;-Lactamase-Positive Enterobacterales from the ATLAS Global Surveillance Program. Karlowsky, JA., Hackel, MA., Stone, GG., et al.[2023]

Ceftibuten-ledaborbactam etzadroxil is an oral treatment that effectively inhibits 89.7% of multidrug-resistant Enterobacterales at a low concentration (MIC90 of 0.25 μg/mL), showing promise against various resistant strains.

The combination demonstrated high efficacy against specific resistant genotypes, inhibiting 96.3% of CTX-M-9 group isolates and 85.9% of KPC-positive isolates, indicating its potential as a valuable option for treating complicated urinary tract infections caused by resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten-Ledaborbactam Activity against Multidrug-Resistant and Extended-Spectrum-&#946;-Lactamase-Positive Clinical Isolates of Enterobacterales from a 2018-2020 Global Surveillance Collection. Karlowsky, JA., Wise, MG., Hackel, MA., et al.[2022]

Ceftibuten is an effective oral cephalosporin antibiotic with broad activity against key respiratory pathogens, including Streptococcus pneumoniae and Haemophilus influenzae, even those producing beta-lactamases.

A single daily dose of 400 mg for adults or 9 mg/kg for children achieves sufficient blood levels to maintain its antibacterial effects throughout most of the dosing period, indicating its potential for convenient treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten: minimal inhibitory concentrations, postantibiotic effect and beta-lactamase stability--a rationale for dosing programs. Neu, HC.[2018]

Ceftibuten is an effective oral antibiotic with a broad spectrum of activity against various gram-negative and some gram-positive bacteria, making it suitable for treating respiratory and urinary tract infections in both adults and children.

It is well-absorbed in the body, has a convenient once-daily dosing schedule, and its safety profile is comparable to other antibiotics, providing a reliable alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten: a new expanded-spectrum oral cephalosporin. Guay, DR.[2019]

Ceftibuten, when combined with SCH 29482, showed additive or indifferent effects against many Gram-positive bacteria and some Gram-negative species, indicating potential for treating various infections.

The combination was effective against most Gram-positive aerobic and anaerobic bacteria responsible for upper respiratory, intraabdominal, and urinary infections, although it exhibited antagonism in certain strains of Serratia marcescens and Citrobacter freundii.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial effects of the combination of ceftibuten and an orally absorbed penem SCH 29482. Chin, NX., Gu, JW., Neu, HC.[2019]

Citations

1. withpower.com withpower.com/trial/phase-1-bacterial-infections-5-2024-fa8c0

Xeruborbactam + Ceftibuten for Bacterial Infection In a study of 131 patients with respiratory and complicated urinary tract infections, oral ceftibuten was found to be as effective as continued parenteral ...

2. journals.asm.org journals.asm.org/doi/10.1128/aac.00857-25

Efficacy of cefiderocol in combination with xeruborbactam ... Taniborbactam restored cefiderocol susceptibility in most isolates (20/21, 95.2%), while xeruborbactam had no effect. Resistance was reversed by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11218443/

In vitro effects of the new oral β-lactamase inhibitor ... Xeruborbactam lowered the MIC90 values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC90 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06079775?term=NCT06079775&rank=1

P1, DDI & MAD PK and Safety Study of Xeruborbactam ... This Phase 1 study will assess if a PK interaction exists between xeruborbactam oral prodrug and ceftibuten when given in combination at doses of each drug that ...

5. clinrol.com clinrol.com/study/NCT06079775

Xeruborbactam Oral Prodrug DDI Study This Phase 1 study will assess if a PK interaction exists between xeruborbactam oral prodrug and ceftibuten when given in combination at doses of each drug that ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10777847/

and multiple-dose study of the pharmacokinetics, safety ... Approximately 60%–70% of an administered dose of ceftibuten is recovered in the urine as unchanged drug (cis-ceftibuten), and a further 10%–20% ...

7. qpexbio.com qpexbio.com/news/qpex-biopharma-announces-presentations-on-phase-1-and-nonclinical-data-on-three-clinical-stage-oral-and-iv-products-targeting-antibiotic-resistant-bacterial-infections-at-2022-id-week-meeting/

Qpex Biopharma Announces Presentations on Phase 1 ... “We will also provide the first presentation of clinical results and PK-PD data from our ORAvance product that delivers xeruborbactam as an oral prodrug with ...