ceftibuten/ledaborbactam etzadroxil (BL/VNRX-7145) / VenatoRx, Basilea - LARVOL DELTA

Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Venatorx Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion

Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Venatorx Pharmaceuticals, Inc. | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Jun 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date

Food Effect on Ceftibuten/VNRX-7145 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Venatorx Pharmaceuticals, Inc. | Enrolling by invitation ➔ Completed | N=36 ➔ 24

Enrollment change • Trial completion

Food Effect on Ceftibuten/VNRX-7145 in Healthy Participants (clinicaltrials.gov) - P1 | N=36 | Enrolling by invitation | Sponsor: Venatorx Pharmaceuticals, Inc. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open

Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Venatorx Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Ceftibuten-Ledaborbactam Activity against Multidrug-Resistant and Extended-Spectrum-β-Lactamase-Positive Clinical Isolates of Enterobacterales from a 2018-2020 Global Surveillance Collection. (PubMed, Antimicrob Agents Chemother) - "In vivo, ledaborbactam etzadroxil (formerly VNRX-7145) is cleaved to the active inhibitor ledaborbactam (formerly VNRX-5236)...At ≤1 μg/mL, ceftibuten-ledaborbactam (MIC, 0.25 μg/mL) inhibited 89.7% of MDR isolates, 98.3% of isolates with a presumptive ESBL-positive phenotype, and 92.6% of trimethoprim-sulfamethoxazole-nonsusceptible, 91.7% of levofloxacin-nonsusceptible, 88.1% of amoxicillin-clavulanate-nonsusceptible, 85.7% of ceftibuten-resistant (MIC >1 μg/mL), and 54.1% of carbapenem-nonsusceptible isolates...Against specific serine carbapenemase genotype-positive isolates, ceftibuten-ledaborbactam inhibited 85.9% of KPC-positive (MIC, 2 μg/mL) and 82.9% of OXA-48-group-positive (MIC, 2 μg/mL) isolates at ≤1 μg/mL. Continued development of ceftibuten-ledaborbactam appears warranted."

Journal • Infectious Disease • Nephrology

In vivo pharmacokinetics and pharmacodynamics of ceftibuten/ledaborbactam, a novel oral β-lactam/β-lactamase inhibitor combination. (PubMed, J Antimicrob Chemother) - "Ledaborbactam fAUC0-24/MIC exposures for stasis were quantified with a ceftibuten human-simulated regimen against β-lactamase-producing Enterobacterales. This study supports the continued development of oral ceftibuten/ledaborbactam etzadroxil (formerly ceftibuten/VNRX-7145)."

Journal • PK/PD data • Preclinical • Infectious Disease • Pneumonia

Food Effect on Ceftibuten/VNRX-7145 in Healthy Participants (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Venatorx Pharmaceuticals, Inc.

New P1 trial

Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Venatorx Pharmaceuticals, Inc.

New P1 trial

Venatorx Pharmaceuticals (BIO 2022) - "Venatorx’s two lead antibacterial clinical-stage programs are intravenous (cefepime-taniborbactam) and oral (ceftibuten/VNRX-7145) broad-spectrum beta-lactam / beta-lactamase inhibitor combinations that are in Phase 3 and Phase 1, respectively. In addition, the first Venatorx antiviral compound (VNRX-9945), a Hepatitis B virus inhibitor, is in Phase 1 clinical development. The Company also has discovery-stage programs targeting a novel class of non-beta-lactam antibiotics called Penicillin Binding Protein (PBP) inhibitors that have the potential to circumvent 70+ years of resistance and usher in a new wave of antibacterial therapeutics."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

In vitro activity of the orally bioavailable ceftibuten/VNRX-7145 (VNRX-5236 etzadroxil) combination against a challenge set of Enterobacterales pathogens carrying molecularly characterized β-lactamase genes. (PubMed, J Antimicrob Chemother) - "VNRX-5236 rescued the in vitro activity of ceftibuten against Enterobacterales carrying common serine β-lactamases, including ESBL, AmpC and the KPC and OXA-48-like carbapenemases. Ceftibuten/VNRX-5236 may have potential as an oral treatment for infections caused by resistant Enterobacterales, while sparing carbapenems."

Journal • Preclinical • Infectious Disease

In Vitro Activity of Ceftibuten/VNRX-5236 against Urinary Tract Infection Isolates of Antimicrobial-Resistant Enterobacterales. (PubMed, Antimicrob Agents Chemother) - "Ceftibuten/VNRX-7145 is a cephalosporin/boronate β-lactamase inhibitor combination under development as an oral treatment for complicated urinary tract infections caused by Enterobacterales producing serine β-lactamases (Ambler class A, C and D)...Each isolate tested was pre-selected to possess a multidrug-resistant (MDR) phenotype that included non-susceptibility to amoxicillin-clavulanate and resistance to levofloxacin...Ceftibuten/VNRX-5236 at concentrations of ≤1, ≤2, and ≤4 μg/ml inhibited 85-89, 89-91, and 91-92% of isolates that were not susceptible (defined by CLSI and EUCAST breakpoint criteria) to nitrofurantoin, trimethoprim-sulfamethoxazole, and/or fosfomycin, (as part of their MDR phenotype), oral agents commonly prescribed to treat uncomplicated urinary tract infections. The potency of ceftibuten/VNRX-5236 (MIC, 2 μg/ml) was similar (within one doubling-dilution) to intravenous-only agents ceftazidime-avibactam (MIC 2 μg/ml) and meropenem-vaborbactam (MIC 1..."

Journal • Preclinical • Infectious Disease • Nephrology • GDF15

Oral Antibiotics in Clinical Development for Community-Acquired Urinary Tract Infections. (PubMed, Infect Dis Ther) - "Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/β-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI...The β-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins...Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy."

Clinical • Journal • Infectious Disease • Nephrology • Pneumonia

[VIRTUAL] Assessment of activity of a novel orally bioavailable β-lactam/β-lactamase inhibitor combination, ceftibuten/VNRX-7145 (VNRX-5236 etzadroxil) against Enteroactberales carrying blaOXA-48 (ECCMID 2021) - No abstract available

Microbiological characterization of VNRX-5236: a broad spectrum β-lactamase inhibitor for rescue of the orally bioavailable cephalosporin ceftibuten as a carbapenem-sparing agent against strains of Enterobacterales expressing extended spectrum β-lactamases and serine carbapenemases. (PubMed, Antimicrob Agents Chemother) - "Rescue of ceftibuten by VNRX-5236 (fixed at 4 μg/mL) in isogenic strains of E. coli expressing class A, C or D β-lactamases demonstrated an expanded spectrum of activity relative to oral comparators including investigational penems, sulopenem and tebipenem. In vivo, whereas ceftibuten alone was ineffective (ED, >128 mg/kg), ceftibuten/VNRX-7145 administered orally protected mice from lethal septicemia caused by K. pneumoniae producing KPC carbapenemase (ED, 12.9 mg/kg). The data demonstrate potent, broad-spectrum rescue of ceftibuten activity by VNRX-5236 in clinical isolates of cephalosporin-resistant and carbapenem-resistant Enterobacterales."

Journal • Infectious Disease • Pneumonia

Oral cephalosporin and β-lactamase inhibitor combinations for ESBL-producing Enterobacteriaceae urinary tract infections. (PubMed, J Antimicrob Chemother) - "A novel cyclic boronic acid β-lactamase inhibitor, QPX7728, was able to produce MIC50 values of 0.5 and ≤0.06 mg/L when paired with cefpodoxime and ceftibuten, respectively. Other novel combinations, cefpodoxime/ETX0282 and ceftibuten/VNRX7145, have also demonstrated excellent activity against ESBL producers. Clinical trials are now awaited."

Journal • Immunology • Nephrology