A Multi-center Interventional Study to Assess Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Full tacrolimus AUC
研究概览
简要总结
Recently, a new prolonged-release tablet version of tacrolimus (Envarsus®) using the so-called MeltDose™ (US Patent No. 7,217,431) drug-delivery technology has been approved as immunosuppressive medication for patients after kidney and liver transplantation in adults but not yet in children. Studies in adults proved that Envarsus® provides the same therapeutic effectiveness as the conventional immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile and reduced peak to trough which might result in reduced tacrolimus dosing and subsequently reduced CNI related toxicity. Furthermore, the once daily formulation might result in improved drug adherence.
The aim of this study is to assess pharmacokinetic profiles of Envarsus® as well as effectiveness and tolerability of this drug in children and adolescents ≥ 8 and ≤ 18 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •caucasian paediatric kidney transplant recipients (single-organ recipients)
- •aged ≥ 8 years but ≤ 18 years who are under tacrolimus (Prograf®) therapy and who are able to swallow tablets with a minimum dose of 0.75 mg / day Envarsus®
- •not less than 6 months after transplantation
- •stable kidney function (delta eGFR < 10 ml/min/1.73 m2 (CKID formula) over the last 3 months)
- •women of childbearing potential and women without childbearing potential
- •patient/parents/legal guardian(s) must be capable of understanding purpose and risks of the study
- •signed informed consent obtained by patient and parents/legal guardians
排除标准
- •coefficient of variation of tacrolimus trough levels > 0.35 over the previous 6 months
- •pregnancy/breast feeding
- •instable kidney function
- •hypersensitivity to any of the components of the medications used
- •not eligible for any reason according to the investigator's valuation
- •known positive HIV-1 or HCV test
- •participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
研究组 & 干预措施
Group A - Envarsus followed by Prograf
4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf)
干预措施: Envarsus® (Drug)
Group A - Envarsus followed by Prograf
4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf)
干预措施: Prograf (Drug)
Group B - Prograf followed by Envarsus
4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus)
干预措施: Envarsus® (Drug)
Group B - Prograf followed by Envarsus
4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus)
干预措施: Prograf (Drug)
结局指标
主要结局
Full tacrolimus AUC
时间窗: 4 weeks
full tacrolimus AUC calculated from Tac measures before administration of drug and 1.5, 2, 4, 6, 8, 12, 13.5, 14, 16, 20, 24 hours after administration of drug at the time point of 2 weeks (14±7 days) after end of build-up period for each patient under both treatments within two time periods with each a length of 4 weeks
次要结局
- Pharmacodynamic analysis(4 weeks)
- eGFR (CKiD formula)(4 weeks)
- Pharmacogenetic analysis(4 weeks)
- Taxonomy of the gut microbiome(10 weeks)
- Tacrolimus trough levels(4 weeks)
- Number of adverse events or toxicity per patient(10 weeks)
- Doses of prolonged-release tacrolimus(4 weeks)
- Number of patients with adverse event or toxicity(10 weeks)
- Treatment failure rate(10 weeks)
- limited sampling strategy (LSS)(4 weeks)
- Gut microbial metabolism(10 weeks)