Plasma and Intrapulmonary Pharmacokinetics of Ceftibuten and Ledaborbactam in Healthy Adults (18-55 Years)
A Phase 1, Open-label Study to Evaluate the Safety and Plasma and Intrapulmonary Pharmacokinetics of Ceftibuten and Ledaborbactam in Healthy Adult Participants
This was a Phase 1, open-label, single-center Pharmacokinetic (PK) study to evaluate plasma and intrapulmonary pharmacokinetics (PK) of ceftibuten and ledaborbactam in healthy adult participants.
Approximately 31 participants were planned to be enrolled in two groups, with approximately 25 in Group 1 and approximately six in Group 2.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In Group 1, participants were to receive a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours. Following the fifth dose, each participant was to undergo one standardized bronchoscopy with bronchoalveolar lavage (BAL) at one of five designated timepoints (2, 4, 6, 8, and 12 hours), with five participants assigned to each timepoint.
In Group 2, participants were to receive a total of five doses of 600 mg oral ceftibuten alone every 12 hours. After the last dose, each participant was to undergo one standardized bronchoscopy with BAL at one of two designated timepoints (4 and 12 hours), with three participants assigned to each timepoint.
Blood samples to determine plasma concentrations of ceftibuten, ledaborbactam etzadroxil (Group 1 only), and urea were to be collected at the designated timepoints.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Phoenix, Arizona, United States, 85032
- Pulmonary Associates
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Participants must have met the following key criteria to be eligible for enrollment into the study:
Inclusion Criteria:
- Healthy adults 18-55 years
- Males or non-pregnant, non-lactating females
- Body Mass Index: ≥18 and ≤32 kg/m2
- Forced expiratory volume in 1 second of at least 80% of predicted value
- Laboratory values meeting defined entry criteria
Exclusion Criteria:
- History of drug allergy or hypersensitivity to penicillin, cephalosporin, or β-lactam antibacterial drug or to medications used during a bronchoscopy
- Conditions that potentially alter absorption and/or excretion of orally administered drugs
- History or presence of significant diseases, including any clinically relevant acute illness or surgery within the past 3 months
- 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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Group 1
Participants in Group 1 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth dose of ceftibuten-ledaborbactam etzadroxil.
|
Five doses of ledaborbactam etzadroxil administered orally every 12 hours
Five doses of ceftibuten administered orally every 12 hours
|
|
Experimental: Group 2
Participants in Group 2 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth of dose of ceftibuten alone.
|
Five doses of ceftibuten administered orally every 12 hours
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The PK parameter AUC0-12 for ceftibuten and ledaborbactam etzadroxil was assessed by standardized bronchoscopy with bronchoalveolar lavage (BAL). BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). Mean concentration values at each BAL sampling time point were determined, and data from all sampling times were combined into a single dataset to calculate the AUC0-12 value for each matrix. AUC 0-12 was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the pharmacokinetic parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma Maximum Concentration (Cmax) of Ceftibuten
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The pharmacokinetic parameter (PK) Cmax of ceftibuten assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma Area Under the Curve From Time Zero to 12 Hours (AUC0-12) for Ceftibuten
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The PK parameter AUC0-12 for ceftibuten assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma Maximum Concentration (Cmax) of Ledaborbactam Etzadroxil
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The pharmacokinetic parameter (PK) Cmax of ledaborbactam etzadroxil assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma AUC0-12h for Ledaborbactam Etzadroxil
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The pharmacokinetic parameter (PK) AUC0-12h of ledaborbactam etzadroxil assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
Drug penetration ratio of epithelial lining fluid (ELF) to unbound plasma were assessed using the AUC values for each matrix for BAL 1 and BAL 2. BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). All pharmacokinetic parameters (PK) were estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the PK parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Ratios of Drug Exposure for Ceftibuten
Time Frame: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
Drug penetration ratio of epithelial lining fluid (ELF) to unbound plasma were assessed using the AUC values for each matrix for BAL 1 and BAL 2. BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). All pharmacokinetic parameters (PK) were estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the PK parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Time Frame: Up to Day 8
|
A TEAE was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug.
|
Up to Day 8
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VNRX-7145-105
- HHSN272201600029C (Other Grant/Funding Number: National Institute of Allergy and Infectious Diseases)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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