A Phase IIa Proof of Concept Study to Explore the Efficacy, Tolerability and Safety of Fosmidomycin Sodium When Administered With Piperaquine Tetraphosphate to Adults and Older Children With Acute Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 主要终点
- Per protocol, PCR-corrected cure rate on Day 28
研究概览
简要总结
The objective of this study is to explore the role of fosmidomycin and piperaquine as non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when administered over three days.
Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by meeting the three key parameters of having different modes of action and different biochemical targets while exhibiting independent blood schizonticidal activity. Like the artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active against existing drug-resistant parasites. Piperaquine has a long half life protecting fosmidomycin as a much shorter lived molecule against selection of resistant parasites and will provide post-treatment prophylaxis.
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
- 1 Year 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects aged 1 to 60 years inclusive
- •Body weight between 5kg and 90kg inclusive
- •Acute manifestations of a mono-infection with Plasmodium falciparum as determined by either a rapid diagnostic test for adults or microscopically confirmed by an asexual parasitaemia of 1,000 to 150,000/uL and fever with an axillary temperature of > 37.5 degress C or oral/rectal/tympanic temperature of > 38.0 degrees C or history of fever during the previous 72 hours
- •Compliance with contraceptive measures throughout the study period of 63 days in females of child bearing potential
排除标准
- •To be eligible for inclusion in the study, subjects must NOT meet any of the following criteria:
- •Signs of severe/complicated malaria according to WHO criteria
- •Pregnancy as excluded by negative serum human chorionic gonadotrophin (hCG) test
- •Lactation
- •Mixed Plasmodium infection
- •Severe vomiting on three or more occasions in the previous 24 hours
- •Severe diarrhoea on four or more occasions in the previous 24 hours
- •Concomitant disease masking assessment of response including
- •abnormal liver function tests with bilirubin > 40 µmol/L, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) levels > x 2 upper limit of normal
- •impaired renal function with creatinine level > x 2 upper limit of normal
- •haemoglobin level < 7.5g/dl
- •white cell count > 12000/µL
- •History of cardiovascular disease including arrhythmia with QTc interval ≥ 450msec, respiratory disease including active tuberculosis, hepatic disease including jaundice, renal failure, malignancy, neurological disorders including convulsions and psychiatric disturbances
- •History of immunological disease including Hepatitis A, B and C and HIV-AIDS
- •Severe malnutrition
- •History of hypersensitivity or adverse reactions to fosmidomycin, piperaquine, artesunate and mefloquine
- •Treatment with antimalarial and antibacterial agents within the previous 28 days
研究组 & 干预措施
Fosmidomycin-Piperaquine
Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days
干预措施: Fosmidomycin-Piperaquine (Drug)
结局指标
主要结局
Per protocol, PCR-corrected cure rate on Day 28
时间窗: 28 days
Six-hourly asexual counts until negative on three successive occasions. Weekly smears on days 7, 14, 21 and 28
次要结局
- Adverse event recording(28 days)
- Per protocol, PCR-corrected cure rates on Day 7 and Day 63(63 days)
- Derived parasite reduction ratio at 48 hours(2 days)
- Parasite clearance time(96 hours)
- Fever clearance time(96 hours)
- Proportion of subjects with gametocytes on Day 7(7 days)