Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Parasite burden in lesions and extralesional tissues.
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics of miltefosine in children and adults with cutaneous leishmaniasis in plasma and intracellularly, and its relation with the parasitologic response. The results will provide pharmacologic bases to optimize the use of miltefosine for the treatment of cutaneous leishmaniasis, and will provide the knowledge base to assess the impact of pharmacokinetic behavior in children and adults on the emergence of drug resistance.
详细描述
An open-label phase IV clinical trial of miltefosine, designed to evaluate intracellular and plasma drug pharmacokinetics in children and adults using a population pharmacokinetics design. Two study groups have been defined: 1) children 2-12 years of age (n=30) and 2) adults 18-60 years of age (n=30) with confirmed parasitological diagnosis of cutaneous leishmaniasis. The participants will receive supervised standard treatment with miltefosine: 1.8 - 2.5 mg/Kg of weight for 28 days.
Miltefosine concentration will be determined in plasma and Peripheral Blood Mononuclear Cell (PBMCs), from 3 or 10ml peripheral blood samples in children and adults respectively. Sampling will be conducted pre-dosing at days 0,1,15 and 29 during treatment, and at months 1, 2, 3 and 6 post-treatment.
A population pharmacokinetics analysis will be performed using a non-linear model of mixed effects with the software Nonlinear Mixed-effects Model (NONMEM), R and Piranha. Parasite burden will be determined by 7SLRNA Quantitative Polymerase Chain Reaction (qPCR) of Leishmania from swab samples of lesions and extralesional tissues before and at the end of treatment. The relationship between pharmacokinetics and parasite persistence/burden will be determined by correlation analysis and pharmacodynamic modeling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 2-12 years of age, or 18-60 years of age
- •Weight greater than 10 kg
- •Parasitologic confirmation of cutaneous leishmaniasis
- •Normal hepatic and kidney function
排除标准
- •Pregnant or lactating women, and women who are planning to conceive during the study or that reject the use of birth control methods.
- •Use of drugs with antileishmanial potential during the previous 6 months, including pentavalent antimonials, amphotericin B, miltefosine, and pentamidine
- •Mucocutaneous or visceral leishmaniasis
- •For female children, menses or other evidence of reproductive maturity
研究组 & 干预措施
Miltefosine
Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days
干预措施: Miltefosine (Drug)
结局指标
主要结局
Parasite burden in lesions and extralesional tissues.
时间窗: Participants will be followed up to 26 weeks
Intracellular and plasma concentration of miltefosine
时间窗: Participants will be followed up to 26 weeks.
次要结局
未报告次要终点