Safety and PK of Ceftibuten-ledaborbactam Etzadroxil Fixed-dose Combination

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, three-part, study in approximately 96 healthy adult participants between 18 and 55 years of age (both inclusive) (16 participants in Part 1, 20 participants in Part 2 and , and approximately 60 participants in Part 3). 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 , 43 days for Part 2 and 83 days for Part 3. All participants in Parts I und 2 will be screened within 28 days prior to dosing. All participants in Part 3 will be screened within 33 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. Participants in Part 3 will also return to the clinic for follow-up assessments 28 days ± 2 days and 42 days ± 2 days after the last dose of study intervention.

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics; Healthy Volunteer; Safety; Drug-Drug Interaction (DDI); FDC
• Intervention / Treatment: Drug: Ledaborbactam etzadroxil; Drug: Ceftibuten; Drug: Ceftibuten-ledaborbactam etzadroxil; Drug: Esomeprazole; Drug: amoxicillin-clavulanate

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Karine Litherland, PhD; Phone Number: +41616061111; Email: Karine.Litherland@basilea.com

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Recruiting
      • ICON, Clinical Research Phase I Unit
      • Contact: Daniel Dickerson, MD. PhD, FAAFP; Phone Number: 913-205-4397; Email: Daniel.Dickerson@iconplc.com
      • Principal Investigator: Daniel Dickerson, MD, PhD, FAAFP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adult male or female, between 18 and 55 years of age
• Body mass index ≥ 18 and ≤ 32 kg/m2
• Laboratory values meeting defined laboratory ranges
• Males or non-pregnant, non-lactating females

Exclusion Criteria:

• History of any hypersensitivity reaction following administration of a cephalosporin, penicillin, or other β-lactam antibacterial drug
• Any acute illness or surgery within the past 3 months determined by the investigator to be clinically relevant
• Positive alcohol, drug or tobacco use/test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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 (FDC) capsules; (c) Ceftibuten-ledaborbactam etzadroxil as FDC capsules after 5 days of esomeprazole orally once daily	Drug: Ledaborbactam etzadroxil; capsules; Drug: Ceftibuten; capsules; Drug: Ceftibuten-ledaborbactam etzadroxil; Fixed Dose Combination (FDC); Drug: Esomeprazole; 40 mg capsule
Experimental: Part 2 Group 1; Part 2 Group 1 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil FDC capsules for 7 days (Fasted Group)	Drug: Ceftibuten-ledaborbactam etzadroxil; Fixed Dose Combination (FDC)
Experimental: Part 2 Group 2; Part 2 Group 2 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil FDC capsules for 7 days (Fed Group)	Drug: Ceftibuten-ledaborbactam etzadroxil; Fixed Dose Combination (FDC)
Experimental: Part 3 (Groups 1, 2, 4, 5, 6); Part 3 will enroll up to 50 participants. Each will receive oral doses of ceftibuten and/or ledaborbactam etzadroxil capsules (combined as FDC when administered together) in fed conditions	Drug: Ledaborbactam etzadroxil; capsules; Drug: Ceftibuten; capsules
Active Comparator: Part 3 Group 3; Part 3 Group 3 will enroll up to 10 participants. Each will receive oral doses of amoxicillin-clavulanate	Drug: amoxicillin-clavulanate; 500 mg-125 mg oral doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Plasma PK AUC0-∞ (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)	Area under the concentration time curve from time zero to infinity (AUC0-∞)	0 - 48 hours on days 1, 4 and 11
Part 1 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)	Maximum observed concentration (Cmax)	0 - 48 hours on days 1, 4 and 11
Proportion of participants of Part 2 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Day 1 thru Day 18 (+/-1)
Proportion of participants of Part 3 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Day 1 thru Day 49 (± 2 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2 Plasma PK AUC0-12h (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)	Area under the concentration time curve from time zero to 12h (AUC0-12h)	Day 1 and Day 7
Part 2 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)	Maximum observed concentration (Cmax)	Day 1 and Day 7
Proportion of participants of Part 1 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.	Day 1 thru Day 18 (+/-1)
Part 3 Plasma PK AUC0-Tau (ceftibuten and/or ledaborbactam)	Area under the concentration time curve from time zero to Tau (AUC0-Tau)	At Day 1 and Day 7
Part 3 Plasma PK Cmax (ceftibuten and/or ledaborbactam)	Maximum observed concentration (Cmax)	At Day 1 and Day 7

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Study Director: Kamal Hamed, MD, Basilea Pharmaceutica International Ltd, Allschwil

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Ceftibuten; Ledaborbactam etzadroxil
• Additional Relevant MeSH Terms: 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amides; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Clavulanic Acid; Clavulanic Acids; Cephalosporins; Thiazines; Omeprazole; Ampicillin; Penicillins; Amoxicillin; Ceftibuten; Amoxicillin-Potassium Clavulanate Combination; Esomeprazole
• Other Study ID Numbers: VNRX-7145-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No