Ceftibuten-ledaborbactam Etzadroxil for Healthy Subjects

Overseen By Venatorx Clinical Science

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Venatorx Pharmaceuticals, Inc.

Disqualifiers: Hypersensitivity to β-lactams, Acute illness, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and processing of a new treatment combination called ceftibuten-ledaborbactam etzadroxil (an antibiotic combination) in healthy adults. Participants in different groups will receive this treatment in varying forms and conditions, such as with or without food. Researchers seek to understand how the body handles the drug, which could inform future treatments. This study suits healthy adults aged 18-55 who have no known allergies to certain antibiotics and do not smoke or use drugs. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy adults, it's possible that taking certain medications might exclude you from participating. It's best to discuss your specific medications with the trial organizers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the drug ceftibuten-ledaborbactam etzadroxil has undergone safety testing in humans. In one study, 82% of participants who received the drug experienced some side effects after starting treatment. These side effects also appeared in 78% of the placebo group, indicating that the side effects were not significantly higher in those taking the drug. Another study found that mild stomach issues were common, occurring in 27.5% of those taking the drug compared to 14.8% of those on placebo.

These side effects were mild and did not lead to serious problems. As this is a Phase 1 trial, the main goal is to assess the treatment's safety and how the body processes it. So far, the safety profile appears manageable, with mild side effects similar to those seen in people not taking the drug. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ceftibuten-ledaborbactam etzadroxil because it combines two active ingredients that could enhance the effectiveness against bacterial infections, particularly those resistant to standard antibiotics. Ceftibuten is a well-known cephalosporin antibiotic, while ledaborbactam etzadroxil acts as a novel beta-lactamase inhibitor, potentially overcoming resistance mechanisms that limit current treatments. Unlike existing antibiotics, this fixed-dose combination could offer a more robust defense against stubborn bacterial strains, providing a new option for patients where traditional antibiotics fall short. This innovative approach not only targets the bacteria more effectively but also aims to simplify treatment with a convenient oral administration.

What evidence suggests that Ceftibuten-ledaborbactam Etzadroxil could be effective?

Research has shown that a new drug combination, ceftibuten-ledaborbactam etzadroxil, could effectively treat bacterial infections. The trial will test this combination in healthy subjects to assess its safety and pharmacokinetics. Studies have found that this combination successfully targets bacteria unresponsive to other antibiotics. Previous research demonstrated that using ceftibuten with ledaborbactam etzadroxil is safe for healthy adults, suggesting it might work well without causing major side effects. Specifically designed to combat hard-to-treat bacterial strains, this combination is undergoing testing. Although more information is needed, early results are promising for its potential use against resistant infections. ^{1 2 3 5 6}

Who Is on the Research Team?

Kamal Hamed, MD

Principal Investigator

Basilea Pharmaceutica International Ltd, Allschwil

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-55 with a BMI between 18 and 32 kg/m2. Participants must have lab values within specific ranges and cannot be pregnant or breastfeeding. The study excludes anyone not meeting these health criteria.

Inclusion Criteria

I am a male or a female not pregnant or breastfeeding.

Body mass index ≥ 18 and ≤ 32 kg/m2

Laboratory values meeting defined laboratory ranges

Exclusion Criteria

Positive alcohol, drug or tobacco use/test

I haven't had any significant illness or surgery in the last 3 months.

History of any hypersensitivity reaction following administration of a cephalosporin, penicillin, or other β-lactam antibacterial drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment Part 1

Participants receive a single oral dose of ceftibuten and ledaborbactam etzadroxil in different sequences

11 days

In-patient stay at CRU

Treatment Part 2

Participants receive oral doses of Ceftibuten-ledaborbactam etzadroxil as fixed-dose capsules for 7 days

7 days

In-patient stay at CRU

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ceftibuten-ledaborbactam Etzadroxil

Trial Overview The study tests a fixed-dose combination of Ceftibuten-ledaborbactam etzadroxil, comparing it to Ledaborbactam etzadroxil, Ceftibuten, and Esomeprazole alone. It's designed to assess safety and how the body processes these drugs in two parts over roughly six weeks.

How Is the Trial Designed?

Group I: Part 2 Group 3 Experimental Treatment 1 Intervention

Part 2 Group 3 will possibly enroll 10 participants. Following availability of PK and safety data from Groups 1 and 2, a determination will be made regarding whether or not Group 3 is needed and the dosing conditions that apply

Group II: Part 2 Group 2 Experimental Treatment 1 Intervention

Part 2 Group 2 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil as fixed-dose capsules for 7 days (Fed Group)

Group III: Part 2 Group 1 Experimental Treatment 1 Intervention

Part 2 Group 1 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil as fixed-dose capsules for 7 days (Fasted Group)

Group IV: Part 1 Experimental Treatment 4 Interventions

Part 1 will enroll at least 16 participants who will receive a single oral dose of ceftibuten and ledaborbactam etzadroxil following a 10-hour fast on 3 occasions in a fixed sequence: (a) Ceftibuten and ledaborbactam etzadroxil as separate capsules; (b) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules after 5 days of esomeprazole orally once daily

Who Is Running the Clinical Trial?

Venatorx Pharmaceuticals, Inc.

Lead Sponsor

Trials

15

Recruited

1,200+

Basilea Pharmaceutica

Lead Sponsor

Trials

53

Recruited

9,900+

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Published Research Related to This Trial

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-β-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 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]

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]

Ledaborbactam, a novel β-lactamase inhibitor, effectively restores the activity of ceftibuten against ceftibuten-resistant Enterobacterales, as demonstrated in a murine thigh infection model using 12 clinical isolates.

The study quantified the necessary ledaborbactam exposure levels for achieving bacteriostasis, indicating promising potential for the oral combination of ceftibuten and ledaborbactam in treating infections caused by multidrug-resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo pharmacokinetics and pharmacodynamics of ceftibuten/ledaborbactam, a novel oral β-lactam/β-lactamase inhibitor combination. Fratoni, AJ., Avery, LM., Nicolau, DP., et al.[2023]

Ceftibuten is an effective oral antibiotic for treating upper and lower respiratory tract infections, as well as urinary tract infections, and is stable against certain resistant bacteria, making it a reliable option for various infections.

The drug has a favorable safety profile similar to other cephalosporins, is well-absorbed (75-90%), and can be dosed once a day, which simplifies treatment regimens for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftibuten: an overview. Owens, RC., Nightingale, CH., Nicolau, DP.[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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40762486/

Safety and pharmacokinetics of single and multiple doses of ... Safety and pharmacokinetics of single and multiple doses of ledaborbactam etzadroxil with or without ceftibuten in healthy volunteers.

2. journals.asm.org journals.asm.org/doi/10.1128/aac.00210-25

Safety and pharmacokinetics of single and multiple doses of ... Safety and pharmacokinetics of single and multiple doses of ledaborbactam etzadroxil with or without ceftibuten in healthy volunteers. This ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06733675

Study Details | NCT06733675 | Safety and PK of Ceftibuten ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

4. venatorx.com venatorx.com/wp-content/uploads/2024/11/Venatorx_IDWeek-2024_CTB-LED-E_Poster_P-1243_final.pdf

Evaluation of Single and Multiple Dose Safety and ... Study 102 (NCT04877379) was a three-part randomized study evaluating the safety and pharmacokinetics of LED-E and ceftibuten (CTB) in healthy adults. • In Part ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12406654/

Pharmacokinetics and safety of single and repeat doses ... This study evaluated the safety and pharmacokinetics of ceftibuten in healthy adults at anticipated higher doses required, in combination with ...

6. academic.oup.com academic.oup.com/ofid/article/12/Supplement_1/ofae631.1425/7987747

P-1243. Evaluation of Single and Multiple Dose Safety and ... Evaluation of Single and Multiple Dose Safety and Pharmacokinetics of Ledaborbactam Etzadroxil and Ceftibuten ... Safety was assessed by recording ...