Pharmacokinetics of Liposomal Amphotericin B (AmBisome®) Given Intravenously to Patients Undergoing Bariatric Surgery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Area Under Curve (AUC) 0-inf Ambisome
研究概览
简要总结
Dosing guidelines for liposomal amphotericin B (AmBisome) in (morbidly) obese patients are not available. Subsequently, the pharmacokinetic profile of AmBisome in this specific patient population is still largely unknown.
To build a valid pharmacokinetic model, obese patients with a BMI ≥ 40 undergoing endoscopic gastric bypass surgery will receive a single dose of 1 mg/kg or 2 mg/kg AmBisome (besides standard anti-bacterial prophylaxis) and a PK-curve will be drawn. These PK-values can then be compared to the pharmacokinetics of a normal-weight group.
详细描述
- The overall trial design is a prospective, open-label, non-randomized, single-centre, single-dose, multiple dose level trial, (1 mg/kg and 2 mg/kg).
- A total of sixteen patients with a BMI ≥40 kg/m2 undergoing bariatric surgery who receive a pre-surgery dose of AmBisome 1 mg/kg (n=8) or 2 mg/kg (n=8) will be enrolled.
- After enrollment of group 1 (1 mg/kg), an interim analysis on the safety of AmBisome will be performed before proceeding to group 2 (2 mg/kg).
- Infusion time and concentration of AmBisome will be 45 minutes (1 mg/kg group) and 90 minutes (2 mg/kg group)
- A PK curve will be determined after administration of a single, pre-surgery dose of AmBisome at t = 0.5, 0.75 (end of infusion group 1), 1.5 (end of infusion group 2), 2, 4, 6, 8, 10, 12, 24, 36, and 48 and (if feasible) 72 hours post infusion (n=12 samples) for group 1 (1 mg/kg), 8 patients.The PK curve of group 2 (2 mg/kg, 8 patients) will be similar to group 1, except for the t=1.5 hour sampling point, which will be end of infusion due to the infusion time of 90 minutes.
- Patients are considered to have completed the study if at least 9/11 samples of the PK curve up until 48 hours have been collected.
- Patients will be selected by the research team to have a good spread in weight bands.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patient has a BMI ≥40 kg/m2 and is undergoing bariatric surgery
- •Subject is at least 18 of age on the day of screening.
- •Subject or legal representatives are able and willing to sign the Informed Consent before screening evaluations.
排除标准
- •Documented history of sensitivity to medicinal products or excipients similar to those found in the polyene preparation.
- •History of, or current abuse of drugs, alcohol or solvents (up until a maximum of three months before enrolment).
- •Inability to understand the nature of the trial and the procedures required.
- •Administration of nephrotoxic medication (aminoglycosids, immunosuppressants, antivirals, antineoplastic agents) up until a maximum of one month before enrolment.
研究组 & 干预措施
Obese Subjects 1mg/kg
8 obese subjects will receive 1mg/kg Ambisome i.v. infused over 45 minutes
干预措施: Administration of study drug (Drug)
Obese Subjects 2mg/kg
8 obese subjects will receive 2mg/kg Ambisome i.v. infused over 90 minutes
干预措施: Administration of study drug (Drug)
结局指标
主要结局
Area Under Curve (AUC) 0-inf Ambisome
时间窗: at t = 0.5, 0.75, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 and (if feasible) 72 hours post infusion
The primary outcome measurement will be the area under the plasma concentration-time curve (AUC) from time 0 to infinitive (inf) post infusion (AUC0- inf) value of AmBisome. This will be determined by use of the log-linear trapezoidal rule.
次要结局
- Peak Plasma Concentration (Cmax) Ambisome(at t = 0.5, 0.75, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 and (if feasible) 72 hours post infusion)