An Open-label Clinical Trial to Assess the Pharmacokinetics and Safety of Miltefosine Allometric Dose for the Treatment of Children With Primary Visceral Leishmaniasis in Eastern Africa
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Pharmacokinetics Parameters (Css/Cmax)
研究概览
简要总结
This is a multicenter, non-comparative, open-label clinical trial to assess the Pharmacokinetics (PK) and safety of miltefosine using an allometric dose algorithm in the treatment of children with primary Visceral Leishmaniasis (VL) in eastern Africa. Efficacy and Pharmacodynamics (PD) will be assessed as secondary outcomes.
The proposed study aims to assess whether drug exposure in children can be increased to equivalent adult drug exposure by using the miltefosine allometric dose given BID for 28 days in paediatric VL patients aged 4-12y and whether this dose is tolerable. The present study is also expected to provide the basis for minimum time to reach sufficient drug exposure for miltefosine activity to guide optimal treatment duration to be used in combination therapy for visceral leishmaniasis. The PK data will be assessed in this trial using a compartmental population PK approach.
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
- 4 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with clinical signs and symptoms of VL and confirmatory parasitological microscopic diagnosis
- •Patients aged > 4 to < 12 years who are able to comply with the study protocol.
- •Patients for whom written informed consent has been signed by parents(s) or legal guardian
- •Weight < 30 kg
排除标准
- •Patients who are relapse cases
- •Patients who have received any anti-leishmanial drugs in the last 6 months
- •Patients with severe malnutrition (for children aged <5 years, weight-for-height WHO reference curves by gender, z score <-3; for children 5-12 years, BMI-for-age WHO reference curves for gender, z score < -3)
- •Patients with positive HIV diagnosis
- •Patients with previous history of hypersensitivity reaction to miltefosine
- •Patients suffering from a concomitant severe infection such as Tuberculosis (TB) or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication
- •Patients suffering from other conditions associated with splenomegaly such as schistosomiasis
- •Pregnant or lactating women or female patient in childbearing age (reached menarche)
- •Patients with haemoglobin < 5g/dl
- •Patients with White Blood Cells (WBC) < 1 x 10³/mm³
- •Patients with platelets < 40,000/mm³
- •Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
- •Patients with bilirubin more than 1.5 times the upper normal range
- •Patients with serum creatinine above the upper limit of normal (ULN) for age and gender.
- •Patients with clinical signs of severe VL disease such as jaundice and bleeding
- •Patients who cannot comply with the planned scheduled visits and procedures of the study protocol
研究组 & 干预措施
Miltefosine
allometric dosing
干预措施: Miltefosine (Drug)
结局指标
主要结局
Pharmacokinetics Parameters (Css/Cmax)
时间窗: Day 28
Pharmacokinetics Parameters (Area Under the Curve (AUC) - composite outcome)
时间窗: During treatment, at 1 and 6 months follow-up
Area Under the Curve calculation is based on several timepoints from first drug intake up to complete elimination of the drug.
Safety (composite outcome) adverse events
时间窗: until day 210
1. Frequency of Serious Adverse Events (SAEs) and Adverse Events (AEs) requiring treatment discontinuation, 2. Frequency and severity of adverse events
次要结局
未报告次要终点