A Phase 1, Open-label Study to Evaluate the Safety and to Characterize the Pharmacokinetics of a Fixed-Dose Combination Formulation of Ceftibuten-Ledaborbactam Etzadroxil

This is a Phase 1, open-label, two-part, study in approximately 46 healthy adult participants between 18 and 55 years of age (both inclusive) (at least 16 participants in Part 1 and up to 30 participants in Part 2). The study will be conducted at one clinical site in the United States. Participants in Part 1 and Part 2 may be conducted in parallel. The duration of an individual participation will be approximately 46 days for Part 1 and 43 days for Part 2. All participants will be screened within 28 days prior to dosing. They will be admitted to the clinical research unit (CRU) the day prior to dosing and will remain in the CRU until the end of the PK sample collection period. All participants will return to the clinic for follow-up assessments 7 days ± 1 day after the last dose of study intervention.

开始日期2025-01-07

申办/合作机构

Venatorx Pharmaceuticals, Inc.

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100 项与 Ledaborbactam Etzadroxil 相关的临床结果

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100 项与 Ledaborbactam Etzadroxil 相关的转化医学

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100 项与 Ledaborbactam Etzadroxil 相关的专利（医药）

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项与 Ledaborbactam Etzadroxil 相关的文献（医药）

2024-12-05·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten

Article

作者: Patel, Robin ; Fowler, Vance G. ; Six, David A. ; Abdelhamed, Ayman M. ; Hujer, Andrea M. ; Hujer, Kristine M. ; Moeck, Greg ; Bethel, Christopher R. ; Good, Caryn E. ; Rhoads, Daniel D. ; Marshall, Steven H. ; Jacobs, Michael R. ; Bonomo, Robert A. ; Uehara, Tsuyoshi ; Mack, Andrew R. ; Papp-Wallace, Krisztina M. ; van Duin, David

ABSTRACT:

Ledaborbactam (formerly VNRX-5236), a bicyclic boronate β-lactamase inhibitor with activity against class A, C, and D β-lactamases, is under development as an orally bioavailable etzadroxil prodrug (VNRX-7145) in combination with ceftibuten for the treatment of urinary tract infections. At ceftibuten breakpoints of ≤1 mg/L (EUCAST) and ≤8 mg/L (CLSI), 92.5% and 99.0%, respectively, of 200 carbapenem-resistant Klebsiella pneumoniae isolates, predominantly K. pneumoniae carbapenemase producing, were susceptible to ceftibuten-ledaborbactam (ledaborbactam tested at a fixed concentration of 4 mg/L) compared to 4.5% and 30.5%, respectively, to ceftibuten alone.

2024-11-01·CLINICAL MICROBIOLOGY AND INFECTION

A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intra-abdominal infections

Article

作者: Zelasky, Michael T ; Breen, Jeanne D ; Akinapelli, Karthik ; Dunne, Michael W ; Das, Anita F ; Breen, Jeanne ; Aronin, Steven I ; Aronin, Steven I. ; Dunne, Michael W. ; Das, Anita F. ; Puttagunta, Sailaja ; Zelasky, Michael T.

OBJECTIVE:

To demonstrate the non-inferiority of intravenous (IV) sulopenem to IV ertapenem, each followed by an oral regimen, in adults with complicated intra-abdominal infections (cIAI).

METHODS:

Hospitalized adults with cIAI were randomly assigned to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid twice daily or 5 days of IV ertapenem followed by oral ciprofloxacin/metronidazole or amoxicillin-clavulanate depending on baseline pathogen susceptibility. The target treatment duration was 7-10 days. The primary (FDA [Food and Drug Administration]-specified) endpoint was clinical response at day 28 (test-of-cure) in the micro-modified intent-to-treat (micro-MITT) population.

RESULTS:

A total of 674 patients were randomly assigned. The two treatment arms were well balanced. Escherichia coli (395 patients) and Bacteroides fragilis (111 patients) were the most frequently isolated pathogens. Clinical success rates in the micro-MITT population were 81.9% (204/249) for sulopenem-treated patients and 87.9% (233/265) for ertapenem-treated patients. The lower bound of the CI for the treatment difference of the primary endpoint was below the pre-specified non-inferiority margin of -10.0 (treatment difference -6.0%, 95% CI, [-12.2 to 0.2]). In all other analysis populations, the lower limit of the 95% CI was above -10.0. Treatment-emergent adverse events (all, 26.0% [87/335] vs. 23.4% [78/333]; related, 6.0% [20/335] vs. 5.1% [17/333]) were similar for sulopenem and ertapenem, respectively. Most events were mild to moderate in severity. There were more serious adverse events in the sulopenem arm (7.5% [25/335] vs. 3.6% [12/333]), only two of which were considered possibly drug-related.

DISCUSSION:

Sulopenem IV followed by oral sulopenem etzadroxil/probenecid was not non-inferior to ertapenem followed by oral step-down in treating cIAI in the micro-MITT population. This finding should be interpreted in the context of country regulations, as endpoint timing, primary analysis population and non-inferiority margin may vary regionally. Both IV and oral sulopenem were well-tolerated; the oral formulation allowed patients with resistant pathogens to step-down from IV therapy.

100 项与 Ledaborbactam Etzadroxil 相关的药物交易

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