A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Long-Term Safety and Tolerability of Tacrolimus in Stable Pediatric Liver Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 主要终点
- Minimum Observed Concentration of Tacrolimus (Cmin)
研究概览
简要总结
A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable pediatric liver transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
详细描述
A 1 arm study to assess the pharmacokinetics, and long-term safety and effectiveness of a modified release tacrolimus based immunosuppression regimen in stable pediatric liver transplant patients converted from a Prograf® based immunosuppression regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is currently receiving Prograf® based immunosuppressive therapy for liver transplantation.
- •Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable
排除标准
- •Patient has previously received an organ transplant other than a liver
- •Patient is currently receiving sirolimus immunosuppression therapy.
研究组 & 干预措施
Tacrolimus MR
Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.
干预措施: tacrolimus modified release (MR) (Drug)
Tacrolimus MR
Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.
干预措施: tacrolimus (Drug)
结局指标
主要结局
Minimum Observed Concentration of Tacrolimus (Cmin)
时间窗: Day 7 at 12 hours post-dose (tacrolimus) and Day 14 at 24 hours post-dose (tacrolimus MR).
The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.
Patient Survival
时间窗: From enrollment until the end of study (up to 54 months).
Patient survival was defined as any participant known to be alive at the end of the study.
Graft Survival
时间窗: From enrollment until the end of study (up to 54 months).
Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant) or participant death.
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
时间窗: For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 and AUC 12-24 for the morning and afternoon doses.
次要结局
- Time to Maximum Observed Concentration of Tacrolimus (Tmax)(For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.)
- Time to Event for Patient Non-survival(From enrollment until the end of study (up to 54 months).)
- Time to Event for Graft Non-survival(From enrollment until the end of study (up to 54 months).)
- Time to First Biopsy-confirmed Acute Rejection(From enrollment until the end of study (up to 54 months).)
- Maximum Observed Concentration of Tacrolimus (Cmax)(For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.)
- Percentage of Participants With Biopsy-confirmed Acute Rejection(From enrollment until the end of study (up to 54 months).)
- Grade of Biopsy-confirmed Acute Rejection Episodes(From enrollment until the end of study (up to 54 months).)
- Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection(From enrollment until the end of study (up to 54 months).)
- Number of Participants With Multiple Rejection Episodes(From enrollment until the end of study (up to 54 months).)
- Number of Participants With Clinically Treated Acute Rejection Episodes(From enrollment until the end of study (up to 54 months).)
- Number of Participants With Chronic Rejection(From enrollment until the end of study (up to 54 months).)
- Number of Participants With Treatment Failure(From enrollment until the end of study (up to 54 months).)
- Primary Reason for Graft Loss(From enrollment until the end of study (up to 54 months).)
- Safety as Assessed by Clinical Signs and Symptoms, Laboratory Parameters and Diagnostic Tests(From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 54 months).)