A Phase 1, Open-label, Multiple-dose, Single Centre Study to Investigate the Effect of Administration of CAZ-AVI and CXL on the Intestinal Flora of Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Changes in the intestinal flora of healthy subjects after administration of ceftazidime-avibactam (CAZ-AVI) and ceftaroline fosamil -avibactam (CXL).
研究概览
简要总结
The purpose of this study is to investigate the effect of administration of CAZ-AVI and CXL on the intestinal flora of male and female healthy volunteers after multiple administrations over 7 days. An assessment of the effect on intestinal flora is an important aspect to understand for the safe clinical use of the investigational products and is expected by regulatory agencies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated, written informed consent prior to any study specific procedures
- •Healthy male and female volunteers aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
- •Females: Female healthy volunteers are authorised to participate in this study if both of the following criteria are met:
- •A negative serum pregnancy test BOTH at screening AND at admission to the study centre.
- •Agrees not to attempt pregnancy while receiving investigational product and for a period of 7 days after last investigational product administration, and agrees to the use of acceptable methods of contraception (according to instructions) prior to, during, and for 7 days after the last investigational product administration.
- •Have a body mass index (BMI) between 19 and 30 kg/m2.
排除标准
- •History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically significant abnormalities in physical examination, ECG, clinical chemistry, haematology, coagulation, or urinalysis results, as judged by the investigator.
- •Pregnant or breastfeeding female healthy volunteers.
- •History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the results or the healthy volunteer's ability to participate in the study.
- •Known history of Clostridium difficile infection in last 3 months.
研究组 & 干预措施
CAZ-AVI or CXL
Cohort 1: CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) by intravenous infusion given over 2 hours, every 8 hours
Cohort 2: CXL (600 mg ceftaroline fosamil and 600 mg avibactam)
干预措施: CAZ-AVI (Drug)
CAZ-AVI or CXL
Cohort 1: CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) by intravenous infusion given over 2 hours, every 8 hours
Cohort 2: CXL (600 mg ceftaroline fosamil and 600 mg avibactam)
干预措施: CXL (Drug)
结局指标
主要结局
Changes in the intestinal flora of healthy subjects after administration of ceftazidime-avibactam (CAZ-AVI) and ceftaroline fosamil -avibactam (CXL).
时间窗: Change from baseline (Day-1) at Day 2, 5, 7, 10, 14 and 21
The number and types of microorganisms in faeces.
次要结局
- Pharmacokinetics of CAZ-AVI in healthy volunteers(Days 1, 2 and 5: Pre-dose and 2 hours post dose. Day 7: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 12, and 24 hours post dose (Day 8))
- Safety and tolerability(Screening up to 12 days after discharge from study site)
- To measure CAZ-AVI and CXL plasma and faecal concentrations using bioactivity techniques.(Day -1, 2, 5, 7, 10, 14 and 21)
- To describe the in vitro susceptibility of new colonizing bacteria of the intestinal microflora to CAZ-AVI and CXL during and after CAZ-AVI and CXL administration.(Day -1, 2, 5, 7, 10, 14 and 21)
- Pharmacokinetics of CXL in healthy volunteers(Days 1, 2 and 5: Pre-dose and 1 hour post dose. Day 7: pre-dose, 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 5, 7, 8, 12, and 24 hours post dose (Day 8))