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, 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.

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

• Study Type: Interventional
• Enrollment (Estimated): 46
• 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

4

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 capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination 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 as fixed-dose 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 as fixed-dose capsules for 7 days (Fed Group)	Drug: Ceftibuten-ledaborbactam etzadroxil; Fixed Dose Combination (FDC)
Experimental: Part 2 Group 3; 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	Drug: Ceftibuten-ledaborbactam etzadroxil; Fixed Dose Combination (FDC)

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)

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)

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): June 30, 2026
• Study Completion (Estimated): June 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): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

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; Amides; beta-Lactams; Lactams; Cephalosporins; Thiazines; Omeprazole; Ceftibuten; 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