Evaluation of Fosmidomycin and Clindamycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria.
研究概览
简要总结
The aim of this study is to evaluate the role of clindamycin and artesunate as possible combination partners for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile
详细描述
The scientific rationale for the use of this combination is to inhibit the ability of the parasite to synthesise isoprenoids, as precursors of many essential compounds including sterols, carotenoids and ubiquinones. This is effected through blockade of the non-mevalonate pathway by fosmidomycin as a potent inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase coupled with targeting of protein biosynthesis by azithromycin through binding to the 50S ribosomal subunit. This mode of action contrasts with the ability of the human host to utilise the mevalonate pathway for isoprenoid synthesis and accounts for the safety profiles of both drugs through the mechanism of selective toxicity. Moreover it affords protection against cross resistance with existing chemotherapeutic agents.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male and female subjects aged 15 to 55 years
- •body mass index ≥ 18.5kg/M2
- •uncomplicated P falciparum malaria with acute manifestations
- •asexual parasitaemia between 500uL and 100,000uL
- •ability to tolerate oral therapy
- •able to give informed signed consent
排除标准
- •signs of severe malaria, according to WHO criteria
- •body mass index ≤ 18.5kg/M2
- •pregnancy by history or by positive urine test
- •lactation
- •mixed plasmodial infection
- •concomitant disease masking assessment of response, including diabetes,
- •uncontrolled hypertension, heart failure, hepatic dysfunction (alanine-amino transferase >150 U/L), renal impairment (creatinine >125umol/L or 3mg/dl)
- •haemoglobin < 8g/dl
- •white cell count > 12000/uL
- •anti-malarial treatment within previous 28 days
- •symptomatic AIDS
研究组 & 干预措施
single arm
Fos-clin/Arte
干预措施: Fosmidomycin (Drug)
结局指标
主要结局
Efficacy of fosmidomycin and clindamycin/artesunate when co-administered to adults with acute uncomplicated P.f. malaria.
时间窗: 12 months
次要结局
- To determine the viability and infectivity of gametocytes induced by the co-administration of fosmidomycin with clindamycin or with clindamycin plus artesunate to adult subjects with acute uncomplicated Plasmodium falciparum malaria.(12 months)