Population Pharmacokinetics Study of Benznidazole in Children With Chagas'Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Pharmacokinetics Endpoints
研究概览
简要总结
The purpose of this study is to describe the population pharmacokinetics parameters of benznidazole in children with acute or early chronic indeterminate form of Chagas Disease.
详细描述
Treatment of Chagas disease (CD) has been always focused on pediatric population. Initially, treatment was recommended only to acute and congenital cases (including newborns diagnosed at birth), with good parasitological response of 60% to 85% of patients in the acute phase and more than 90% of congenitally infected infants treated in the first year of life.
Despite existing treatment recommendations for children with CD (from birth to 12y), there is no formulation available that meets the needs of target pediatric population, especially the younger age groups. Benznidazole (Bz), developed over 30 years ago and the main drug of choice, is only available in an 'adult' tablet strength of 100 mg (LAFEPE Benznidazol®).
With the lack of pediatric formulation, the 100mg tablet needs to be fractionated in ½ and ¼ tablets or prepared as extemporaneous formulations (macerated, diluted, suspension, etc) to adjust the dose to patient weight, often leading to sub or over-dosing, which may affect safety and efficacy of the treatment. With regards to children, there is an absolute lack of information on Bz PK in the pediatric population and its relationship with treatment safety and efficacy.
In order to respond to the need of a age-adapted, easy to use pediatric formulation, DNDi and LAFEPE have joined efforts to develop a 12.5 mg dispersible Bz tablet targeting treatment of CD in children < 20 Kg. Once this formulation is available, two pharmacokinetics studies are planned to be conducted: a comparative bioavailability study in adult healthy normal volunteers and a population pharmacokinetics study in young children.
The group of newborns, from birth to - 2 years-old children, has been included as they represent the population of congenital cases. Current estimates of positive serology for CD in women at reproductive age vary considerably from country-to-country ranging from 5-40%, with vertical transmission rates of up to 12%. There is consensus that congenital infection may remain an important mode of transmission for another generation, and appropriate treatment targeting newborns is a possible control strategy (with very high chances of cure) with the new pediatric formulation.
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 Day 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between newborn (1day) - 12 years
- •Diagnosis of T. cruzi infection by:
- •Direct microscopic examination or
- •Conventional serology, at least two positive tests (ELISA, IIF or HAI)
- •Written informed consent form by parent/ legal representative
- •Children assent if > 7 years
排除标准
- •Pre-term (< 37 weeks gestational age) or weight < 2500 g
- •Female subject who has reached menarche
- •Subjects presenting any other acute or chronic health conditions, that in the opinion of the PI, may interfere with the PK, efficacy and/or safety evaluation of the study drug
- •Known history of hypersensitivity or serious adverse reactions to nitro- imidazoles
- •History of CD treatment with benznidazole or nifurtimox in the past
- •Immunocompromised patients (clinical history compatible with HIV infection, primary immunodeficiency or prolonged treatment with corticosteroids or other immunosuppressive drugs)
- •Abnormal laboratory test values at screening for the following parameters: total WBC count, platelet count, ALT, AST, total bilirubin and creatinine.
- •Exception for this criterion is considered for newborns with congenital Chagas Disease, for whom ALT/AST and bilirubin will not be considered exclusion criteria unless considered clinically significant by the investigator.
- •Inability to comply with follow-up and/or not having a permanent address
- •Any condition that prevents the subject from taking oral medication
结局指标
主要结局
Pharmacokinetics Endpoints
时间窗: Day 60
Plasma level concentrations of benznidazol determined in children at first day of treatment (Day 0), steady state phase (D7 and Day 30) and at the end of treatment (Day 60). Population pharmacokinetics parameters of benznidazole in children, including CL, Vd, and Ka. Individual AUC. Individual Cmax. Individual Cmin. Individual t1/2 will be estimated using population parameters.
次要结局
- Efficacy Endpoints(Day 60)
- Safety Endpoints(Day 60)
- Safety endpoints(Day 60)