A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Safety and Tolerability of Tacrolimus in Stable Kidney 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 kidney transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
详细描述
This is a Phase II open-label, multi-center conversion study in stable, adult kidney transplant recipients to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable kidney transplant patients converted from a 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 kidney 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 kidney
- •Patient is currently receiving sirolimus immunosuppression therapy.
研究组 & 干预措施
Tacrolimus Modified Release
Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
干预措施: Tacrolimus Modified Release (MR) (Drug)
Tacrolimus Modified Release
Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 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: For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 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 trapezoidal rule.
Maximum Observed Concentration (Cmax) of Tacrolimus
时间窗: For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Minimum Concentration of Tacrolimus (Cmin)
时间窗: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.
The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose.
Time to Maximum Observed Concentration of Tacrolimus (Tmax)
时间窗: For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Patient Survival
时间窗: From enrollment until the end of study (up to 60 months).
Patient Survival defined as any participant who did not die by 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 permanent return to dialysis (for more than 30 days)) or participants death.
次要结局
- Percentage of Participants With Biopsy-confirmed Acute Rejection(From enrollment until the end of study (up to 60 months).)
- Change From Baseline in Creatinine Clearance(Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).)
- Time to Event for Patient Non Survival(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).)
- Grade of Biopsy-confirmed Acute Rejection Episodes(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).)
- Number of Participants With Treatment Failure(From enrollment until the end of study (up to 60 months).)
- Change From Baseline in Serum Creatinine(Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).)
- Primary Reason for Graft Loss(From enrollment until the end of study (up to 60 months).)
- Number of Participants Returning to Permanent Dialysis(From enrollment until the end of study (up to 60 months).)
- Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs(From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).)