A Phase 2, Open-Label, Multi-Center Study to Assess the Pharmacokinetics, Long-term Safety and Tolerability of Tacrolimus in Stable 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
- 70
- 主要终点
- Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
研究概览
简要总结
A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
详细描述
A one arm study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 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
After enrollment in the pharmacokinetic period, patients were maintained on their usual dose of tacrolimus twice daily on Day 1 through Day 14 and on Day 15 were converted to tacrolimus modified release (MR) once-daily in the morning for 14 days, converted back to tacrolimus twice daily for 14 days and then converted back to tacrolimus MR formulation once-daily in the morning for 14 days, all based on a 1:1 mg for mg total daily dose conversion. The extended treatment period began on day 57 and consisted of a single dose of tacrolimus extended-release formulation once every morning through the end of the study.
Dose adjustments were allowed in order to maintain the target tacrolimus trough level within the range of 5 to 20 ng/mL and for clinical reasons.
干预措施: tacrolimus modified release (MR) (Drug)
Tacrolimus MR
After enrollment in the pharmacokinetic period, patients were maintained on their usual dose of tacrolimus twice daily on Day 1 through Day 14 and on Day 15 were converted to tacrolimus modified release (MR) once-daily in the morning for 14 days, converted back to tacrolimus twice daily for 14 days and then converted back to tacrolimus MR formulation once-daily in the morning for 14 days, all based on a 1:1 mg for mg total daily dose conversion. The extended treatment period began on day 57 and consisted of a single dose of tacrolimus extended-release formulation once every morning through the end of the study.
Dose adjustments were allowed in order to maintain the target tacrolimus trough level within the range of 5 to 20 ng/mL and for clinical reasons.
干预措施: tacrolimus (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
时间窗: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 for the morning (0-12 hour) and afternoon (12-24 hour) doses.
Patient Survival
时间窗: From enrollment until the end of study (up to 60 months).
Patient survival was defined as any participant known to be alive at the time of analysis.
Graft Survival
时间窗: From enrollment until the end of study (up to 60 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.
Minimum Observed Concentration of Tacrolimus (Cmin)
时间窗: Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for 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.
次要结局
- Maximum Observed Concentration of Tacrolimus (Cmax)(Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.)
- Time to Maximum Observed Concentration of Tacrolimus (Tmax)(Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.)
- Percentage of Participants With Biopsy-confirmed Acute Rejection(From enrollment until the end of study (up to 60 months).)
- Time to Event for Patient Non-survival(From enrollment until the end of study (up to 60 months).)
- Number of Participants With Treatment Failure(From enrollment until the end of study (up to 60 months).)
- Time to Event for Graft Non-survival(From enrollment until the end of study (up to 60 months).)
- Time to First Biopsy-confirmed Acute Rejection(From enrollment until the end of study (up to 60 months).)
- Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection(From enrollment until the end of study (up to 60 months).)
- Number of Participants With Multiple Rejection Episodes(From enrollment until the end of study (up to 60 months).)
- Number of Participants With Clinically Treated Acute Rejection Episodes(From enrollment until the end of study (up to 60 months).)
- Number of Participants With Chronic Rejection(From enrollment until the end of study (up to 60 months).)
- Primary Reason for Graft Loss(From enrollment until the end of study (up to 60 months).)
- Change From Baseline in Total Bilirubin(Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).)
- Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs(From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 60 months).)
- Grade of Biopsy-confirmed Acute Rejection Episodes(From enrollment until the end of study (up to 60 months).)
- Change From Baseline in Alanine Aminotransferase (ALT)(Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).)
- Change From Baseline in Aspartate Aminotransferase (AST)(Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).)