Population Pharmacokinetics of Cefiderocol During Acute Pulmonary Exacerbations in Adult Patients With Cystic Fibrosis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Clearance
研究概览
简要总结
There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Cefiderocol is a newly approved broad spectrum intravenous siderophore cephalosporin antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia, all pathogens implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of cefiderocol in 12 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of cefiderocol 2 grams infused over 3 hours every 6-8 hours, depending on kidney function. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of cefiderocol. Safety and tolerability will be assessed throughout the 2 day study.
详细描述
Participants will receive 4-6 doses of cefiderocol 2 grams every 6-8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of nine blood samples will be collected to measure cefiderocol concentrations. Data will be fit to a population pharmacokinetic model. The final model will be utilized in a Monte Carlo simulation to determine the probability of several different dosing regimens retaining concentrations above the minimum inhibitory concentration (MIC) for at least 75% of the dosing interval. These data will be utilized to determine an optimized dosing regimen for adults with CF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of CF
- •Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment
排除标准
- •Females that are pregnant and/or breastfeeding
- •History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful re-exposure is not a contraindication)
- •History of a lung transplant at any time in the past or any other organ transplantation (e.g., liver) within the last 6 months
- •Moderate to severe renal dysfunction defined as a creatinine clearance < 60 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis
- •A hemoglobin less than 8 gm/dL at baseline
- •Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)
研究组 & 干预措施
Cefiderocol
Participants will receive intravenous cefiderocol at a dosing regimen consistent with the current prescribing information and according estimated renal function. Each dose will be infused over 3 hours.
干预措施: Cefiderocol (Drug)
结局指标
主要结局
Clearance
时间窗: 0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose
This outcome determines the clearance of cefiderocol over the dosing interval.
Volume of Distribution
时间窗: 0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose
This outcome determines the volume of distribution of cefiderocol over the dosing interval.
次要结局
- Probability of Target Attainment at 4 mcg/mL(24 hours)
研究者
Joseph L. Kuti, PharmD
Associate Director, CAIRD
Hartford Hospital