Relationships Between Pharmacokinetic and Pharmacodynamic Strategies for Assessment of the Risks for Acute Rejection and Side Effects of Mycophenolate Mofetil
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 主要终点
- Percentage of Participants With Acute Rejection
研究概览
简要总结
This study will evaluate the correlation between the pharmacokinetic and pharmacodynamic parameters of CellCept in patients undergoing primary kidney transplantation, in order to assess the impact on clinical outcome and the risks of acute rejection. All patients will receive oral CellCept, 1g twice daily, and pharmacokinetic and pharmacodynamic parameters will be measured at weeks 2, 4, 12 and 24. The anticipated time on study treatment is 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Adult patients, 18 to 65 years of age
- •Patients undergoing primary kidney transplantation
排除标准
- •Recipients of multiple organ transplants
- •Prior therapy with CellCept
- •Presence or history of malignancies, except for successfully treated basal or squamous cell carcinoma of the skin
- •Active peptic ulcer or active serious digestive system disease that may affect the absorption of CellCept
研究组 & 干预措施
Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
干预措施: mycophenolate mofetil (Drug)
Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
干预措施: antibody induction (Drug)
Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
干预措施: Cyclosporine (Drug)
Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
干预措施: corticosteroid (Drug)
结局指标
主要结局
Percentage of Participants With Acute Rejection
时间窗: Day 1, Weeks 2, 4, 12, 24, and 28
Diagnosis of acute rejection was suspected in any participant with an increase in serum creatinine greater than or equal to (≥) 25 percent (%). All suspected acute rejections were confirmed by biopsy. The start date of acute rejection was identified as the date of biopsy.
Time to Rejection
时间窗: Day 1, Weeks 2, 4, 12, 24, and 28
The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)
时间窗: Day 1, Weeks 2, 4, 12, 24, and 28
BPAR was defined according to 1997 Banff Criteria as a biopsy Banff grade of IA, IB, IIA, IIB, or III. Grade IA was defined as significant interstitial infiltration with greater than (\>)25% of parenchyma affected, and foci of moderate tubulitis with \>4 mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IB was defined as significant interstitial infiltration with \>25% parenchyma affected, and foci of severe tubulitis with \>10% mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IIA was defined as mild to moderate intimal arteritis. Grade IIB was defined as severe intimal arteritis comprising \>25% of the luminal area. Grade III was defined as transmural arteritis and/or arterial fibrinoid changes and necrosis of medial smooth muscle cells.
次要结局
- Percentage of Participants With Hematologic Toxicity(BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up))
- Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity(BL and Weeks 2, 4, 12, and 24)
- Percentage of Participants With Graft Loss(Day 1, Weeks 2, 4, 12, 24, and 28)
- Percentage of Participants Surviving(Day 1, Weeks 2, 4, 12, 24, and 28)
- Total Mycophenolate Acid (MPA) by Visit and Timepoint(Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits)
- Free MPA (mcg/mL) by Visit(Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits)
- MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit(Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28))
- Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint(BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits)
- IMPDH Expression I by Visit and Timepoint(BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits)
- IMPDH Expression II by Visit and Timepoint(BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits)
- Interleukin 8 (IL-8) Expression by Visit and Timepoint(BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits)
- Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint(BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits)
- Percentage of Participants With Infection(BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up))
- Percentage of Participants With Gastrointestinal Toxicities(BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit))
- Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection(BL and Weeks 2, 4, 12, and 24)
- Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity(BL and Weeks 2, 4, 12, and 24)