A Phase 1, Open-label Study to Evaluate the Safety and Plasma and Intrapulmonary Pharmacokinetics of Ceftibuten and Ledaborbactam in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Intrapulmonary PK - AUC0-12 (ceftibuten)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Group 1
Participants in Group 1 will undergo one standardized bronchoscopy with bronchoalveolar lavage after the fifth dose of ceftibuten-ledaborbactam etzadroxil.
干预措施: ledaborbactam etzadroxil (Drug)
Group 1
Participants in Group 1 will undergo one standardized bronchoscopy with bronchoalveolar lavage after the fifth dose of ceftibuten-ledaborbactam etzadroxil.
干预措施: ceftibuten (Drug)
Group 2
Participants in Group 2 will undergo one standardized bronchoscopy with bronchoalveolar lavage after the fifth of dose of ceftibuten alone.
干预措施: ceftibuten (Drug)
结局指标
主要结局
Intrapulmonary PK - AUC0-12 (ceftibuten)
时间窗: 0-12 hours after 5th dose
Area under the curve from time zero to 12 hours
Intrapulmonary PK - AUC0-12 (ledaborbactam)
时间窗: 0-12 hours after 5th dose
Area under the curve from time zero to 12 hours
Plasma PK - Cmax (ceftibuten)
时间窗: 0-12 hours after 5th dose
Maximum concentration
Plasma PK - Cmax (ledaborbactam)
时间窗: 0-12 hours after 5th dose
Maximum concentration
Plasma PK - AUC0-12 (ceftibuten)
时间窗: Time Frame: 0-12 hours after 5th dose
Area under the curve from time zero to 12 hours
Plasma PK - AUC0-12 (ledaborbactam)
时间窗: 0-12 hours after 5th dose
Area under the curve from time zero to 12 hours
Ratios of drug exposure in ELF to plasma using the AUC values for each matrix
时间窗: 0-12 hours after 5th dose
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
时间窗: 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.
Plasma Maximum Concentration (Cmax) of Ceftibuten
时间窗: 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.
Plasma Area Under the Curve From Time Zero to 12 Hours (AUC0-12) for Ceftibuten
时间窗: 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.
Plasma Maximum Concentration (Cmax) of Ledaborbactam Etzadroxil
时间窗: 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.
Plasma AUC0-12h for Ledaborbactam Etzadroxil
时间窗: 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.
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
时间窗: 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.
Ratios of Drug Exposure for Ceftibuten
时间窗: 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.
次要结局
- Proportion of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)(Day 1 - Day 8)
- Proportion of participants discontinuing study drug due to TEAEs and SAEs(Day 1 - Day 8)
- Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil(Up to Day 8)