Characterising the Pharmacokinetics of Tafenoquine Under Fed Conditions for Plasmodium Vivax Radical Cure in Children ≤12kg and >28 Days Old
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Tafenoquine blood concentration-time curve area under the curve from time zero to infinity (AUC[0-∞])
研究概览
简要总结
This study is an open label, single arm, pharmacokinetic trial. A total of 20 participants (children ≤12kg and >28 days old) will be enrolled. Enrollment will be competitive between Thailand and Vietnam study sites (each site will enroll as many patients that are eligible until the sample size is reached). Tafenoquine will be given concomitantly with the schizonticidal agent, chloroquine, on the day of enrolment. The participant will be admitted to hospital for observation and until the malaria smear is negative for asexual parasites on 2 consecutive days or until the schizonticidal treatment is completed, which will be approximately 3-7 days. All treatment doses will be supervised. Follow up will continue on days 7, 14, 21, and 28 then every month until month 4. Parent/guardian of participants will be instructed to follow up in between visits if participants are feeling unwell. Participants who are lost to follow up (any missed visit), who require drug re-administration after vomiting, or where at least 3 pharmacokinetic samples are not successfully drawn, will be replaced. Participants being replaced will continue in the study for safety assessments and to ensure the treatment of recurrences. The total blood drawn for this study will be 3.76 mL if the participant has no recurrences.
详细描述
Objectives:
Primary Objective:
- Characterise the pharmacokinetic profile of tafenoquine in G6PD normal (G6PD activity ≥70%) children ≤12kg and >28 days old with P. vivax mono-infection
Secondary Objectives:
- Characterise the safety and tolerability of tafenoquine in children ≤12kg and >28 days old
- Correlate day 7 methaemoglobin levels to the tafenoquine pharmacokinetic profile
- Correlate the CYP2D6 metaboliser status and genotype with tafenoquine concentrations in vivo
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
盲法说明
This is an open-label study. Investigators, study staff, participants, and parents/guardians are aware of the treatment administered. All drug administrations are directly observed by study staff.
入排标准
- 年龄范围
- 28 Days 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •P. vivax mono-infection as diagnosed by RDT or microscopy
- •Quantitative G6PD activity ≥70%
- •Age >28 days old and weight ≤12kg
- •The parent/guardian can understand the study instructions and provide written informed consent
- •Willing to return with the participant for 4 months to follow up
排除标准
- •Hb < 8 g/dL
- •Severe malaria
- •Blood transfusion in the last 3 months
- •Any previous history of severe anaemia or haemolysis
- •If age is <6 months old today: gestational age at birth <37wk or birth weight <2.5kg
- •Use of tafenoquine within the last 4 months
- •History of allergic response to an 8-aminoquinoline or the nationally recommended schizonticide (e.g., chloroquine, artemether-lumefantrine)
- •Use of drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters, and drugs that affect chloroquine metabolism
- •Presence of any condition which in the judgement of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. chronic disease, failure to thrive, severe malnutrition)
研究组 & 干预措施
Tafenoquine Plus Chloroquine
Participants with Plasmodium vivax malaria will receive oral chloroquine and tafenoquine under direct observation. Chloroquine tablets (250 mg) will be administered at a total dose of 25 mg/kg base divided over 3 days (Days 0, 1, and 2) as schizonticidal treatment. Tafenoquine will be administered as a single oral dose for radical cure according to body weight: 25 mg for participants weighing <5 kg, 50 mg for participants weighing ≥5 kg to <10 kg, and 100 mg for participants weighing ≥10 kg to 12 kg. Participants will be followed for safety, efficacy, pharmacokinetics, and recurrence of P. vivax malaria for 4 months.
干预措施: Tafenoquine (Drug)
Tafenoquine Plus Chloroquine
Participants with Plasmodium vivax malaria will receive oral chloroquine and tafenoquine under direct observation. Chloroquine tablets (250 mg) will be administered at a total dose of 25 mg/kg base divided over 3 days (Days 0, 1, and 2) as schizonticidal treatment. Tafenoquine will be administered as a single oral dose for radical cure according to body weight: 25 mg for participants weighing <5 kg, 50 mg for participants weighing ≥5 kg to <10 kg, and 100 mg for participants weighing ≥10 kg to 12 kg. Participants will be followed for safety, efficacy, pharmacokinetics, and recurrence of P. vivax malaria for 4 months.
干预措施: Chloroquine (Drug)
结局指标
主要结局
Tafenoquine blood concentration-time curve area under the curve from time zero to infinity (AUC[0-∞])
时间窗: days 1, 7, 28 and month 4
The area under the tafenoquine concentration-time curve from time zero to infinity (AUC\[0-∞\]) will be estimated from the concentration-time data.
Maximum observed tafenoquine blood concentration (Cmax)
时间窗: days 1, 7, 28 and month 4
Maximum observed blood concentration (Cmax) will be estimated from the concentration-time data.
Terminal elimination half-life of tafenoquine (t½)
时间窗: days 1, 7, 28 and month 4
Terminal elimination half-life (t½) will be estimated from the concentration-time data.
次要结局
- Number of adverse events and serious adverse events(up to month 4)
- Methaemoglobin levels measured by oximetry(day 7)
- CYP2D6 genotype and associated phenotype as defined by the Clinical Pharmacogenetics Implementation Consortium (CPIC)(up to month 4)