A Phase II, Open-Label, Multi-Center Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From a Prograf® Based Immunosuppressive Regimen to a Tacrolimus Prolonged Release, Advagraf® Based Immunosuppressive Regimen, Including a Long-Term Follow-Up
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 26
- 主要终点
- Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus and Tacrolimus Prolonged Release
研究概览
简要总结
Parts A & B: Conversion of stable pediatric allograft recipients from Prograf® immunosuppression to Advagraf® immunosuppression to compare exposure and one year follow-up for safety and efficacy.
Part C: Continuation of long-term follow-up and provision of ongoing study medication to subjects to whom Advagraf® is currently not available.
详细描述
Part A: On Day 1 subjects will be converted from their routine Prograf®-based immunosuppressive regimen to a Prograf®-based immunosuppressive regimen supplied by the Sponsor as study medication and continue treatment until Day 7. The daily dose of the study medication must be the same [1:1 (mg:mg)] as the Prograf® dose received during the 30-day screening period.
On Day 7 the first 24 hour PK profile will be started. Samples will be taken over a 24 hour period and will be completed on Day 8.
On Day 8 subjects will be switched to once-daily Advagraf® on a 1:1 (mg:mg) total daily dose basis and continue treatment until Day 14.
On Day 14 the second 24-hour PK profile will be started. Samples will be taken over a 24-hour period and will be completed on Day 15.
Part B: One year follow-up period to evaluate safety and efficacy of tacrolimus when administered as an Advagraf®-based immunosuppressive regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be able to swallow intact study medication capsules
- •Received a single solid organ transplant at least 6 months prior to entry into the study
- •The subject's parent(s), or their legal representative(s), has been fully informed and has given written informed consent to participate in the study. The subject has given assent where applicable
- •Has been receiving a Prograf® based immunosuppressive regimen for a minimum of 3 months
- •Negative pregnancy test prior to enrolment (females)
- •Must agree to practice effective birth control during the study
- •Stable whole blood trough levels of tacrolimus in the range of 3.5 - 15ng/mL (+/-0.5ng/mL) and clinically stable in the opinion of the Investigator
排除标准
- •Previously received a multiple organ transplant
- •Any rejection episode within 3 months prior to enrolment or within the last 6 months that required anti-lymphocyte antibody therapy, or 2 or more rejection episodes within the last 12 months
- •Currently receiving Rapamycin, Certican or MPA (Myfortic®)
- •Chronic dysfunction of the allograft, in the opinion of the Investigator
- •Major changes in their immunosuppressive regimen within the last 3 months prior to entry into the study
- •The subject is pregnant or breast feeding
研究组 & 干预措施
Tacrolimus Prolonged Release
Participants receive tacrolimus prolonged release once daily starting from day 1 for 4 weeks for in Part A, and continue to receive tacrolimus prolonged release once daily up to end of Part B of the study.
干预措施: Tacrolimus prolonged release (Drug)
Tacrolimus Prolonged Release
Participants receive tacrolimus prolonged release once daily starting from day 1 for 4 weeks for in Part A, and continue to receive tacrolimus prolonged release once daily up to end of Part B of the study.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus and Tacrolimus Prolonged Release
时间窗: Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
次要结局
- Maximum Concentration (Cmax) of Tacrolimus and Tacrolimus Prolonged Release(Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose)
- Time to Attain Maximum Concentration (tmax) of Tacrolimus and Tacrolimus Prolonged Release(Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose)
- Patient survival(Up to Week 54)
- Number of Participants with Adverse Events (Part B)(From first dose of tacrolimus prolonged release in Part A up to 7 days after last dose of tacrolimus prolonged release in Part B (up to 55 weeks))
- Number of Participants with Acute Rejections(Up to Week 54)
- Number of Participants with Biopsy Proven Acute Rejections (BPARs)(Up to Week 54)
- Graft survival(Up to Week 54)
- Efficacy Failure(Up to Week 54)
- Trough Concentration (C24) for Tacrolimus and Tacrolimus Prolonged Release(Days 7 and 14, 24 hours after dosing)
- Severity of Biopsy Proven Acute Rejection Episodes(Up to Week 54)
- Number of Participants with Adverse Events (Part A)(From first dose of tacrolimus up to 7 days after last dose of tacrolimus prolonged release in Part A (up to 21 days))