Trial Outcomes & Findings for Plasma and Intrapulmonary Pharmacokinetics of Ceftibuten and Ledaborbactam in Healthy Adults (18-55 Years) (NCT NCT06665555)

NCT ID: NCT06665555

Last Updated: 2026-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Results posted on

2026-08-24

Participant Flow

Participants were screened and randomized at one site in the USA

Participant milestones

Participant milestones
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Overall Study
STARTED
28
6
Overall Study
COMPLETED
27
6
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Overall Study
Adverse Event
1
0

Baseline Characteristics

Plasma and Intrapulmonary Pharmacokinetics of Ceftibuten and Ledaborbactam in Healthy Adults (18-55 Years)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=28 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
n=6 Participants
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Total
n=34 Participants
Total of all reporting groups
Age, Continuous
38.4 years
STANDARD_DEVIATION 10.64 • n=1541 Participants
40.7 years
STANDARD_DEVIATION 6.74 • n=1121 Participants
38.8 years
STANDARD_DEVIATION 10.02 • n=2662 Participants
Sex: Female, Male
Female
21 Participants
n=1541 Participants
4 Participants
n=1121 Participants
25 Participants
n=2662 Participants
Sex: Female, Male
Male
7 Participants
n=1541 Participants
2 Participants
n=1121 Participants
9 Participants
n=2662 Participants
Race/Ethnicity, Customized
White
15 Participants
n=1541 Participants
5 Participants
n=1121 Participants
20 Participants
n=2662 Participants
Race/Ethnicity, Customized
Black or African American
7 Participants
n=1541 Participants
1 Participants
n=1121 Participants
8 Participants
n=2662 Participants
Race/Ethnicity, Customized
Asian
2 Participants
n=1541 Participants
0 Participants
n=1121 Participants
2 Participants
n=2662 Participants
Race/Ethnicity, Customized
Other
4 Participants
n=1541 Participants
0 Participants
n=1121 Participants
4 Participants
n=2662 Participants
Race/Ethnicity, Customized
Hispanic Or Latino
6 Participants
n=1541 Participants
3 Participants
n=1121 Participants
9 Participants
n=2662 Participants
Race/Ethnicity, Customized
Not Hispanic Or Latino
22 Participants
n=1541 Participants
3 Participants
n=1121 Participants
25 Participants
n=2662 Participants
Region of Enrollment
United States
28 Participants
n=1541 Participants
6 Participants
n=1121 Participants
34 Participants
n=2662 Participants
Weight
79.07 kg
STANDARD_DEVIATION 12.84 • n=1541 Participants
78.53 kg
STANDARD_DEVIATION 11.98 • n=1121 Participants
78.97 kg
STANDARD_DEVIATION 12.52 • n=2662 Participants
Height
173.2 cm
STANDARD_DEVIATION 9.01 • n=1541 Participants
169.7 cm
STANDARD_DEVIATION 7.20 • n=1121 Participants
172.6 cm
STANDARD_DEVIATION 8.73 • n=2662 Participants
BMI
26.30 kg/m^2
STANDARD_DEVIATION 3.45 • n=1541 Participants
27.27 kg/m^2
STANDARD_DEVIATION 3.75 • n=1121 Participants
26.47 kg/m^2
STANDARD_DEVIATION 3.46 • n=2662 Participants

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations. Only five participants were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=5 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Value for ceftibuten for BAL 1
14867 h*ng/mL
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Value for ceftibuten for BAL 2
10486 h*ng/mL
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Value for ledaborbactam etzadroxil for BAL 1
14529 h*ng/mL
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Value for ledaborbactam etzadroxil for BAL 2
9809 h*ng/mL
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations.

The pharmacokinetic parameter (PK) Cmax of ceftibuten assessed at at steady-state.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=25 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
n=6 Participants
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Plasma Maximum Concentration (Cmax) of Ceftibuten
22708 ng/mL
Standard Deviation 5317
21017 ng/mL
Standard Deviation 9828

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations.

The PK parameter AUC0-12 for ceftibuten assessed at at steady-state.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=25 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
n=6 Participants
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Plasma Area Under the Curve From Time Zero to 12 Hours (AUC0-12) for Ceftibuten
121799 h*ng/mL
Standard Deviation 27105
110962 h*ng/mL
Standard Deviation 46516

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations.

The pharmacokinetic parameter (PK) Cmax of ledaborbactam etzadroxil assessed at at steady-state.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=25 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Plasma Maximum Concentration (Cmax) of Ledaborbactam Etzadroxil
15796 ng/mL
Standard Deviation 2754

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations.

The pharmacokinetic parameter (PK) AUC0-12h of ledaborbactam etzadroxil assessed at at steady-state.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=25 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Plasma AUC0-12h for Ledaborbactam Etzadroxil
70406 ng x h/mL
Standard Deviation 12964

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations. Only five participants were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=5 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Ratio for BAL 1 for ceftibuten
0.341 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Ratio for BAL 2 for ceftibuten
0.239 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Ratio for BAL 1 for ledaborbactam etzadroxil
1.560 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Ratio for BAL 2 for ledaborbactam etzadroxil
1.032 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.

PRIMARY outcome

Timeframe: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose

Population: PK Evaluable Set: all participants who received at least one dose of study drug and had at least one evaluable plasma or BAL concentration. Participants may have been excluded from this set for relevant protocol deviations. Only five participants were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=5 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Ratios of Drug Exposure for Ceftibuten
Ratio for BAL 1 for ceftibuten
0.272 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.
Ratios of Drug Exposure for Ceftibuten
Ratio for BAL 2 for ceftibuten
0.222 Ratio
Standard Deviation NA
It was pre-specified in the study protocol to only calculate an arithmetic mean with no measure of dispersion using Phoenix WinNonlin Non-compartmental analysis.

SECONDARY outcome

Timeframe: Up to Day 8

Population: Safety Set: participants who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=28 Participants
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
n=6 Participants
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Any serious TEAE
0 Participants
0 Participants
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Any non-serious TEAE leading to early termination
1 Participants
0 Participants
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Any non-serious TEAE
2 Participants
0 Participants
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Not any TEAE
25 Participants
6 Participants

Adverse Events

Group 1: Ceftibuten and Ledaborbactam Etzadroxil

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Group 2: Ceftibuten

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Group 1: Ceftibuten and Ledaborbactam Etzadroxil
n=28 participants at risk
Participants received a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours.
Group 2: Ceftibuten
n=6 participants at risk
Participants received a total of five doses of 600 mg oral ceftibuten alone every 12 hours.
Gastrointestinal disorders
Dyspepsia
3.6%
1/28 • 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.
0.00%
0/6 • 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.
Nervous system disorders
Headache
3.6%
1/28 • 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.
0.00%
0/6 • 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.
Psychiatric disorders
Anxiety
3.6%
1/28 • 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.
0.00%
0/6 • 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.

Additional Information

Kamal Hamed, MD

Basilea Pharmaceutica International Ltd, Allschwil

Phone: +41616061111

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60