TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children Receiving Once Weekly Rifapentine and Isoniazid for the Treatment of Latent Tuberculosis Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 47
- 主要终点
- Determine whether rifapentine exposure (level 24 hours after drug ingestion) is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
研究概览
简要总结
Compared to adults, children appear to require higher weight-based doses of rifapentine to acheive comparable drug levels. TBTC Study 26, a study of the effectiveness and tolerability of weekly rifapentine/isoniazid for three months versus daily isoniazid for nine months for the treatment of latent tuberculosis infection, has been amended to include children ages 2-11 based on an initial single-dose study and pharmacokinetic modeling. Study 26PK evaluates the adequacy of the doses chosen for young children enrolled in Study 26 with a single blood draw, 24 hours after the third or subsequent weekly Study 26 dose of rifapentine and isoniazid. An adult control is enrolled for each child enrolled.
详细描述
The pharmacokinetics of rifapentine have been studied in adults, adolescents (ages 12-15 years), and patients with hepatic dysfunction and HIV infection. However, there are no published data on the efficacy, safety or pharmacokinetics of rifapentine in children. This lack of data has precluded till now enrollment of children less than 12 years old in TBTC Study 26, a study of the effectiveness and tolerability of weekly rifapentine/isoniazid for three months versus daily isoniazid for nine months for the treatment of latent tuberculosis infection, a phase 3 treatment trial that will enroll 8000 persons with latent tuberculosis infection. A recently completed initial evaluation of rifapentine pharmacokinetics among children receiving a single dose of rifapentine demonstrated significantly lower exposures of rifapentine among children compared to adults, when children were given weight-based doses chosen to be comparable to a 600 mg oral dose in adults. This reduced exposure suggested that children require higher weight-based doses than adults and a model was constructed to estimate rifapentine doses in children that would result in exposures similar to the 900 mg dose used for adults in Study 26. Study 26 has been amended to include children ages 2-11 based on the initial single-dose study and pharmacokinetic modeling. The purpose of Study 26PK is to evaluate the adequacy of the doses chosen for young children who enrolled in Study 26.
Briefly, this study aims to:
- determine whether rifapentine exposure is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
- correlate rifapentine exposure with toxicity in young children
- validate accuracy of weight-based dosing in children
- determine rifapentine bioavailability in children
- determine association in adults between polymorphisms of MDR1 genotype and rifapentine exposure
- correlate isoniazid concentrations in adults with acetylator status
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in TBTC Study 26 randomized to treatment with once weekly isoniazid and rifapentine:
- •Child between the ages of 2 to less than 12 years for whom informed consent by a guardian and of assent (if applicable) have been obtained.
- •Adult greater than age 18 for whom informed consent has been obtained.
- •Willingness to undergo a blood phlebotomy 24 hours following dosing of isoniazid and rifapentine after receiving at least three once-weekly doses of rifapentine plus isoniazid.
- •If as a result of a contact investigation, both a parent and child are enrolled in Study 26, both may be co-enrolled into the pharmacokinetic substudy with the adult serving as the control for the child. Preference will be given to a biologic parent of the same gender. If no eligible biologic parent is available for study, the next adult of the same gender and at the same TBTC site, who is substudy eligible, will serve as the adult control.
排除标准
- 未提供
结局指标
主要结局
Determine whether rifapentine exposure (level 24 hours after drug ingestion) is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
时间窗: 24 hours after drug ingestion
Rifapentine Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, AUC0-inf
时间窗: 24 hours after study-drug administration; AUC0-inf estimated using a nonlinear mixed-effects pharmacokinetic model incorporating the 24-hour rifapentine concentration, C24.
Rifapentine exposure was estimated in children and adults receiving once-weekly rifapentine plus isoniazid. A sparse sampling design used a plasma sample collected 24 hours after administration of study drugs.
Correlation Between Rifapentine C24 and AUC0-inf
时间窗: 24 hours after study-drug administration
Value represents the coefficient of determination (R-squared) for the relationship between rifapentine C24 and AUC0-inf.
次要结局
- Correlate estimated rifapentine exposure with toxicity in young children receiving rifapentine and isoniazid for latent tuberculosis infection.(During the three months of taking rifapentine)
- Validate the accuracy of estimated rifapentine exposure with pediatric rifapentine dose based on weight.(24 hours after drug ingestion)
- Determine estimated drug bioavailability in pediatric subjects (ages 2 to < 12 years) given higher mg/kg doses of rifapentine.(24 hours after drug ingestion)
- Determine the association in adults between polymorphisms of MDR1 genotype (P-glycoprotein) and rifapentine estimated exposure.(at the time of blood draw)
- Determine the frequency of lower antitubercular drug concentrations in adults with acetylator status determined by N-acetyltransferase genotypes and of rifapentine by C24 and by MDR1 genotypes.(at the time of blood draw)
- Rifapentine AUC0-inf by Tablet Administration Method in Children(24 hours after study-drug administration)