An Open Label, Non-comparative, Multicenter Study to Assess the Pharmacokinetics, Safety and Efficacy of Tafenoquine (SB-252263, WR238605) in the Treatment of Pediatric Subjects With Plasmodium Vivax Malaria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg)
研究概览
简要总结
This is a prospective, open-label, multicenter, non-comparative, single arm study of pediatric subjects with Plasmodium vivax (P. vivax) malaria, aged 6 months to <16 years of age. A total of 60 subjects will be enrolled. Potential subjects who are slide-positive for P. vivax will be started by the site on chloroquine (CQ) per local/national guidelines. Sites will have up to 48 hours to obtain consent. Once full consent is provided, all subjects will be screened and, if eligible, receive Tafenoquine (TQ), given as a single dose on Day 1. All study medication should be taken with food. After the treatment period, subjects will attend up to 7 follow-up visits through Day 120 (Days 3, 8, 15, 29, 60, 90 and 120). The main cohort will consist of subjects aged >=2 years to <16 years with no restriction on gender. Subjects will be dosed according to four weight bands. Within the total of 60 enrolled pediatric subjects, a second cohort of up to 6 infants aged >=6 months to <2 years (weighing >=5 kilogram [kg]) will be recruited following completion of a planned first interim analysis. An interim analysis will be conducted once sufficient data from 16 subjects is available to assess pharmacokinetic (PK) and safety parameters. If needed, a second interim analysis will be conducted after a total of 32 subjects have enrolled. The primary objective of this PK bridging study is to adequately characterize the systemic TQ exposure in the pediatric population in order to identify appropriate doses that achieve a similar exposure to that of the TQ adult dose of 300 milligram (mg).
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
- 6 Months 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is >=2 years to <16 years of age at the time of signing of the assent and/or informed consent. An additional cohort of subjects aged >=6 months to <2 years may be recruited following the first interim analysis.
- •The subject has a positive malarial smear for P. vivax.
- •The subject has a history of fever within 48 hours prior to enrollment.
- •The subject has a glucose 6-phosphate dehydrogenase (G6PD) value (measured by a quantitative spectrophotometric phenotype assay) >=70% of the site median value for G6PD normal adult males.
- •The subject has a screening Hb value >=8 gram per decilitre (g/dL).
- •The subject has a body weight >=5 kg.
- •Males and females are eligible to enter the study. A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of: Non-childbearing potential (i.e., premenstrual); or Child-bearing potential, has a negative pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study medication: Complete abstinence from intercourse for 2 weeks prior to administration of study medication, throughout the study and for a period of 90 days after stopping study medication; Use of combined oral contraceptive consisting of spermicide with either condom or diaphragm; Use of intrauterine device with a documented failure rate of <1% per year; Use of depo provera injection; Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female.
- •The subject and/or the subject's parent(s)/legal guardian(s) agree to G6PD genotyping in the context of a subsequent hemolytic anemia AE.
- •The subject and parent(s)/legal guardian(s) are willing and able to comply with the study protocol.
- •In accordance with regional/local laws and regulations, the parent(s)/legal guardian(s) has given written informed, dated consent; and the subject has given written assent, if applicable, to participate in the study.
排除标准
- •The subject has a mixed malaria infection (identified by a malarial smear or rapid diagnostic test).
- •The subject has a condition that may affect absorption of study medication, such as severe vomiting (no food or inability to take food during the previous 8 hours).
- •The subject has a liver alanine aminotransferase (ALT) >2 time the upper limit of normal (ULN).
- •The subject has a clinically significant concurrent illness (for example; pneumonia, meningitis, septicaemia, coagulopathy, severe hemorrhage), pre-existing condition (e.g., renal disease, malignancy, malnutrition, known pre-existing human immunodeficiency virus [HIV]), febrile convulsions prior to consent, or clinical signs and symptoms of severe cardiovascular disease (for example; congenital heart disease).
- •The subject has a history of porphyria, psoriasis, or epilepsy.
- •The subject has taken anti-malarials (for example; artemisinin-based combination therapies, mefloquine, primaquine, or any other 4- or 8-aminoquinoline) or drugs with antimalarial activity within 30 days prior to study entry.
- •The subject has received treatment with any investigational drug within 30 days of study entry, or within 5 half-lives, whichever is longer.
- •The subject has taken or will likely require during the study the use of: histamine-2 blockers, antacids, anti-diabetic drugs of the biguanide class (i.e., phenformin, buformin), anti-arrhythmic agents dofetilide, procainamide, pilsicainide.
- •The subject has a serum creatinine above the ULN and is currently taking metformin.
- •The subject has a history of allergy or intolerance to chloroquine, mefloquine, tafenoquine, primaquine, or to any other 4- or 8-aminoquinoline.
- •The subject has previously enrolled in this study.
- •The subject has severe P. vivax malaria as defined by world health organization (WHO) criteria
研究组 & 干预措施
Tafenoquine 50 mg
Subjects with weight band of >=5 to <=10 kilogram (kg) will receive 50 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Tafenoquine (Drug)
Tafenoquine 50 mg
Subjects with weight band of >=5 to <=10 kilogram (kg) will receive 50 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Chloroquine (Drug)
Tafenoquine 100 mg
Subjects with weight band of >10 to <=20 kg will receive 100 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Tafenoquine (Drug)
Tafenoquine 100 mg
Subjects with weight band of >10 to <=20 kg will receive 100 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Chloroquine (Drug)
Tafenoquine 150 mg
Subjects with weight band of >10 to <=20 kg will receive 150 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Tafenoquine (Drug)
Tafenoquine 150 mg
Subjects with weight band of >10 to <=20 kg will receive 150 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Chloroquine (Drug)
Tafenoquine 200 mg
Subjects with weight band of >20 to <=35 kg will receive 200 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Tafenoquine (Drug)
Tafenoquine 200 mg
Subjects with weight band of >20 to <=35 kg will receive 200 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Chloroquine (Drug)
Tafenoquine 300 mg
Subjects with weight band of >35 kg will receive 300 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Tafenoquine (Drug)
Tafenoquine 300 mg
Subjects with weight band of >35 kg will receive 300 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines.
干预措施: Chloroquine (Drug)
结局指标
主要结局
Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg)
时间窗: Days 3, 15, 29 and 60 post dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of tafenoquine. Pharmacokinetic parameters were determined using standard non-compartmental methods. AUC(0-infinity) of tafenoquine was evaluated for participants aged \>=2 years to \<16 years (weighing \>=5 kg). Pharmacokinetic (PK) population consisted of all participants with at least one PK sample taken at Days 3, 15, 29 and 60, with accurate dosing and sample time histories.
次要结局
- Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline(Baseline (Day 1) and up to Day 8)
- Number of Participants With Gastrointestinal Adverse Events(Up to Day 120)
- AUC(0-infinity) of Tafenoquine by Weight Band in Participants Aged >=6 Months to <2 Years (Weighing >=5 kg)(Days 3, 15, 29 and 60 post dose)
- Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)(Up to Day 120)
- Number of Participants With Hemoglobin Decline From Baseline Over First 10 Days(Baseline and up to Day 10)
- Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline(Baseline (Day 1) and up to Day 8)
- Number of Participants With Relapse-Free Efficacy at 4 Months(4 months)