Pharmacokinetics of Anidulafungin Given Intravenously as Antifungal Prophylaxis to Recipients of an Allogeneic Haematopoietic Stem Cell Transplant Following Myeloablative Chemotherapy or Patients Receiving Intensive Chemotherapy for AML-MDS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- pharmacokinetics
研究概览
简要总结
The purpose of this study is to study the pharmacokinetics of anidulafungin (Ecalta ®) given intravenously as antifungal prophylaxis to recipients of an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or patients receiving intensive chemotherapy for AML-MDS who are at high risk for developing invasive fungal disease.
详细描述
Alternate dosing strategies of echinocandin drugs might provide a better efficacy in the treatment of fungal infections as compared to the current label dosing strategy. Before conducting a controlled efficacy trial of echinocandins in haematology patients, the pharmacokinetics of these alternate dosing strategies need to be tested before bringing this idea to practice in a large randomised trial.
Therefore we want to conduct a pharmacokinetic study with anidulafungin given every 48 hours or every 72 hours. This research can be performed best in a group of patients at high risk for developing invasive fungal infections.
Recipients of an allogeneic haematopoietic stem cell transplant (HSCT) or patients receiving intensive chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) are at a relatively high risk of developing invasive fungal infections and are therefore candidates for primary prophylaxis. However, the options are limited to fluconazole which affords no protection against mould infections. Amphotericin B is not considered useful because of its desoxycholate formulation has too many side effects and its lipid formulations are too expensive nor have the broad-spectrum triazoles itraconazole and voriconazole proved their value in this setting. Anidulafungin is the first of a new class of antifungal drugs quite unlike any others attacking specifically the ß 1-3 -D-glucan synthase of the cell wall. It has relatively few side effects and appears safe and effective for treating Aspergillus and Candida infections. Since these two genera account for 90% of fungal infections in HSCT recipients the drug would seem an ideal candidate for prophylaxis.
Importantly, nothing is known about the pharmacokinetics of alternate dosing regimens of anidulafungin in this patient population. Therefore a pharmacokinetic study of a homogenous cohort of patients is necessary to test the assumption, that adequate exposure is obtained with alternate dosing and that it is safe.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient receives an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or receives intensive chemotherapy for AML-MDS
- •Subject is at least 18 and not older than 65 years of age on the day of the first dosing
- •Has no signs or symptoms of invasive fungal disease
- •If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant
- •Has an ALAT, ALAT, alkaline phosphatase < 5 times the upper limit of normal and a bilirubin level < 3 times the upper limit of normal
- •Is not known to be hypersensitive to echinocandin antifungal agents
- •Is managed with a quadruple central venous catheter (Arrow-Howes™ Quad-Lumen 8.5,5 French; Arrow International)
- •Subject is 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 anidulafungin preparation
- •Known of Positive HIV test or hepatitis B or C test in history
- •History of QT time prolongation
- •History of or current abuse of drugs, alcohol or solvents
- •Inability to understand the nature of the trial and the procedures required
- •Has not previously participated in this trial
研究组 & 干预措施
group A
Day 1-15: anidulafungin 200 mg q48h IV maintenance dose (8 dosages)
干预措施: anidulafungin 200 mg q48h (Drug)
group B
Day 1-13: anidulafungin 300 mg q72h IV maintenance dose (5 dosages)
干预措施: anidulafungin 300 mg q72h (Drug)
结局指标
主要结局
pharmacokinetics
时间窗: two weeks per subject
comparison of pharmacokinetics of anidulafungin given once in every two days or once in every three days
次要结局
- adequate exposure(2 weeks for each subject; analysis after 3 months after last subject inclusion)
- safety(3 weeks)