A Prospective, Multicenter, Open-Label Study to Assess Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients Admitted With Acute Pulmonary Exacerbation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 4
- 主要终点
- Tazobactam 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. Ceftolozane/Tazobactam is a newly approved broad spectrum intravenous antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of ceftolozane/tazobactam in 20 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 ceftolozane/tazobactam 3 grams every 8 hours. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day study.
详细描述
Participants will receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of six blood samples will be collected to measure ceftolozane and tazobactam 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 39% 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
- •Age 18 years or older
- •Documented diagnosis of CF
- •Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment
- •If female, subjects must be non-pregnant and non-lactating. Females can be either not of a child-bearing potential or if of a child-bearing potential, on acceptable modes of birth control such as abstinence from sexual intercourse, oral/parenteral contraceptives, or barrier method
排除标准
- •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)
- •Prior (within 24 hours of first dose of study drug) or concomitant receipt of piperacillin/tazobactam or probenecid
- •History of lung transplant
- •Moderate to severe renal dysfunction defined as a creatinine clearance < 50 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)
- •Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data
- •Planned or prior participation in any other interventional drug study within 30 days
研究组 & 干预措施
Ceftolozane/Tazobactam
Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses
干预措施: Ceftolozane/Tazobactam (Drug)
结局指标
主要结局
Tazobactam Clearance
时间窗: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the clearance of tazobactam over the 8 hour dosing interval.
Tazobactam Volume of Distribution (Central Compartment)
时间窗: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the volume of distribution of tazobactam over the 8 hour dosing interval.
Ceftolozane Clearance
时间窗: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.
Ceftolozane Volume of Distribution (Central Compartment)
时间窗: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the volume of distribution of ceftolozane over the 8 hour dosing interval.
次要结局
- Ceftolozane Probability of Target Attainment at 8 mcg/ml(24 hours)
研究者
Joseph L. Kuti, PharmD
Associate Director, Clinical and Economic Studies
Hartford Hospital