Pharmacokinetics of Mycophenolate Mofetil in de Novo Lung Allograft Recipients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Cmax of Free MPA at Day 8
研究概览
简要总结
This open-label, single center study will assess the pharmacokinetics, efficacy and safety of mycophenolate mofetil in lung allograft recipients. Participants will be split into 2 groups according to the original disease: Group A (cystic fibrosis) and Group B (chronic obstructive pulmonary disease [COPD], emphysema, idiopathic pulmonary fibrosis, alpha-1 antitrypsin deficiency [A1AD]). All participants will receive mycophenolate mofetil orally, 1.5 grams (g) twice daily (BID) from Day 2 to 30 post transplantation, and 1 g BID from Day 31 to 90 post transplantation. Anticipated time on study treatment is 90 days, and target sample size is 50-100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •primary single or bilateral lung allograft
- •original disease cystic fibrosis, COPD, emphysema, idiopathic pulmonary fibrosis or A1AD
排除标准
- •lung allograft retransplantation
- •multiple organ transplantation
- •severe gastrointestinal disorder
- •malignancies or history of malignancy
研究组 & 干预措施
Mycophenolate Mofetil; Cystic Fibrosis
Participants with cystic fibrosis will receive mycophenolate mofetil 1.5 g, orally (PO), BID from Days 2 through 30 post-transplantation, and 1 g, PO, BID from Days 31 through 90 post-transplantation.
干预措施: mycophenolate mofetil (Drug)
Mycophenolate Mofetil; Other
Participants with COPD, emphysema, idiopathic pulmonary fibrosis, or A1AD will receive mycophenolate mofetil 1.5 g, PO, BID, from Days 2 through 30 post-transplantation, and 1 g, PO, BID from Days 31 through 90 post-transplantation.
干预措施: mycophenolate mofetil (Drug)
结局指标
主要结局
Cmax of Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Cmax was expressed in mcg/L.
Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Dose-normalized Cmax was determined (in 1 per liter \[1/L\]) by dividing the Cmax by the actual dose taken.
Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 after transplantation
Cmax was expressed in milligrams per liter (mg/L).
Cmax of MPA, MPAG and AcMPAG at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Cmax was expressed in mg/L.
Cmax of MPA, MPAG and AcMPAG at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Cmax was expressed in mg/L.
Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Cmax of MPA, MPAG and AcMPAG at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Cmax was expressed in mg/L.
Cmax of Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Cmax was expressed in micrograms per liter (mcg/L).
Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4
时间窗: Predose (0 hour) on Day 4 post-transplantation
Cmin was expressed in mg/L.
Cmin of Free MPA at Day 8
时间窗: Predose (0 hour) on Day 8 post-transplantation
Cmin was expressed in mcg/L.
Cmin of Free MPA at Day 20
时间窗: Predose (0 hour) on Day 20 post-transplantation
Cmin was expressed in mcg/L.
CL of MPA, MPAG and AcMPAG at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
AUC0-12 of Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours times micrograms per liter (hours\*\[mcg/L\]).
AUC0-12 of Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
Cmax of Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Cmax was expressed in mcg/L.
Cmax of Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Cmax was expressed in mcg/L.
Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Cmin of MPA, MPAG and AcMPAG at Day 8
时间窗: Predose (0 hour) on Day 8 post-transplantation
Cmin was expressed in mg/L.
Cmin of Free MPA at Day 4
时间窗: Predose (0 hour) on Day 4 post-transplantation
Cmin was expressed in mcg/L.
Cmin of Free MPA at Day 90
时间窗: Predose (0 hour) on Day 90 post-transplantation
Cmin was expressed in mcg/L.
Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Vz of MPA, MPAG and AcMPAG at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Clearance (CL) of MPA, MPAG and AcMPAG at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in liters per hour (L/hour).
AUC0-12 of MPA, MPAG and AcMPAG at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Cmin of MPA, MPAG and AcMPAG at Day 20
时间窗: Predose (0 hour) on Day 20 post-transplantation
Cmin was expressed in mg/L.
Cmin of MPA, MPAG and AcMPAG at Day 90
时间窗: Predose (0 hour) on Day 90 post-transplantation
Cmin was expressed in mg/L.
Vz of MPA, MPAG and AcMPAG at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
AUC0-12 of MPA, MPAG and AcMPAG at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
AUC0-12 of MPA, MPAG and AcMPAG at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
CL of MPA, MPAG and AcMPAG at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
CL of MPA, MPAG and AcMPAG at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
AUC0-12 of Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
Vz of MPA, MPAG and AcMPAG at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours time milligrams per liter (hours\*\[mg/L\]).
Free Fraction of Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
AUC0-12 of Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
Free Fraction of Free MPA at Day 4
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
MPA Free fraction (in percent \[%\]) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
Free Fraction of Free MPA at Day 20
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
Free Fraction of Free MPA at Day 90
时间窗: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
次要结局
- Forced Vital Capacity (FVC) at Day 90 Post-Transplantation(Day 90 post-transplantation)
- Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels(Baseline, Days 4, 8, 20 and 90 post-transplantation)
- Percent of Predicted FEV1 at Day 90 Post-Transplantation(Day 90 post-transplantation)
- Change From Baseline in T-Cell Phenotype(Baseline, Days 20 and 90 post-transplantation)
- Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation(Day 90 post-transplantation)
- Percentage of Participants With Opportunistic Infections(Up to Day 90)