Safety, Tolerability and Pilot Efficacy of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection
试验速览
- 阶段
- 4 期
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Safety and tolerability as measured by methemoglobin
研究概览
简要总结
This study specifically seeks to provide data on the safety, tolerability and pilot efficacy of short course, high dose primaquine treatment in Papua New Guinean children aged 5-10 years, in a cross-sectional study design. Community screened asymptomatic cases and/or cases of clinically diagnosed malaria admitted to the out-patient units of the health center, will be screened for Glucose-6-phosphate dehydrogenase deficiency (G6PD) and malaria illness by rapid diagnostic test and P. vivax infection confirmed by light microscopy. Following treatment with artemether-lumefantrine (Coartem), G6PD normal children will be enrolled into the study and followed for 2 months. Primaquine treatment will be allocated to study participants in a step-wise design; firstly receiving the current 14 day treatment regimen of 0.5 mg/kg total dose (n=40); secondly, a 7 day treatment regimen receiving a total dose of 1.0 mg/kg/day; then thirdly, receive 1.0 mg/kg twice daily dose (bd) for a total of 3.5 days, should the 7 day treatment prove to be safe and well tolerated. In addition to this dose-escalation study, the pharmacokinetic profiles of single doses of 0.5 mg/kg and 1.0 mg/kg will be determined using an intensive sampling protocol, in children aged 5-10 years. The pharmacokinetic profiles obtained by this sub-study will be essential for modeling the population pharmacokinetic data obtained from the dose-escalation study. As there is currently no data on the safety, tolerability and efficacy of primaquine in children, the present study will validate previous observation and contribute to the knowledge of primaquine as a treatment for liver stages of Plasmodium vivax infection.
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
- 5 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Permanent resident in study area
- •Absence of history of hypersensitivity reactions to pre-treatment drugs
- •Positive for P. vivax infections on blood smear or PCR
- •Normal G6PD enzyme activity
排除标准
- •Features of severe malaria
- •Clinical evidence of nonmalarial illness
- •Severe malnutrition (weight for age nutritional Z score <60th percentile)
- •Moderate to severe anemia (Hb <8g/dL)
- •Permanent disability which prevents or impedes study participation
研究组 & 干预措施
14 day dose regimen
0.5 mg/kg oral Primaquine administered daily for 14 days
干预措施: Primaquine (Drug)
7 day dose regimen
1.0 mg/kg oral Primaquine administered daily for 7 days
干预措施: Primaquine (Drug)
3.5 day dose regimen
1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days
干预措施: Primaquine (Drug)
结局指标
主要结局
Safety and tolerability as measured by methemoglobin
时间窗: 2 months post baseline
Safety and tolerability as measured by hemoglobin
时间窗: 2 months post baseline
Safety and tolerability as measured by liver biochemistry
时间窗: 2 months post baseline
Safety and tolerability as measured by symptom questionnaire
时间窗: 2 months post baseline
次要结局
- Time to first or only clinical Plasmodium vivax episode(2 months from baseline)
- Pharmacokinetics - clearance (CL)(42 days)
- Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen(2 months from baseline)
- Pharmacokinetics - elimination half-life (t1/2)(42 days)
- Pharmacokinetics - volume of distribution (Vd)(42 days)
- Pharmacokinetics - maximal concentration (Cmax)(42 days)
- Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR)(2 months from baseline)
- Pharmacokinetics - area under the curve (AUC)(42 days)