A Study of Mycophenolate Mofetil (CellCept) in Lung Transplant Recipients

Phase 3

Completed

Conditions: Lung Transplantation

Interventions: Drug: mycophenolate mofetil

Registration Number: NCT01014442

Lead Sponsor: Hoffmann-La Roche

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

Inclusion Criteria

primary single or bilateral lung allograft
original disease cystic fibrosis, COPD, emphysema, idiopathic pulmonary fibrosis or A1AD

Exclusion Criteria

lung allograft retransplantation
multiple organ transplantation
severe gastrointestinal disorder
malignancies or history of malignancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mycophenolate Mofetil; Other	mycophenolate mofetil	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.
Mycophenolate Mofetil; Cystic Fibrosis	mycophenolate mofetil	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.

Primary Outcome Measures

Name	Time	Method
Cmax of Free MPA at Day 8	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	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	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	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	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	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	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	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	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	Predose (0 hour) on Day 4 post-transplantation	Cmin was expressed in mg/L.
Cmin of Free MPA at Day 8	Predose (0 hour) on Day 8 post-transplantation	Cmin was expressed in mcg/L.
Cmin of Free MPA at Day 20	Predose (0 hour) on Day 20 post-transplantation	Cmin was expressed in mcg/L.
CL of MPA, MPAG and AcMPAG at Day 90	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	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	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	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	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	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	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	Predose (0 hour) on Day 8 post-transplantation	Cmin was expressed in mg/L.
Cmin of Free MPA at Day 4	Predose (0 hour) on Day 4 post-transplantation	Cmin was expressed in mcg/L.
Cmin of Free MPA at Day 90	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	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	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	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	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	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	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	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	Predose (0 hour) on Day 20 post-transplantation	Cmin was expressed in mg/L.
Cmin of MPA, MPAG and AcMPAG at Day 90	Predose (0 hour) on Day 90 post-transplantation	Cmin was expressed in mg/L.
Vz of MPA, MPAG and AcMPAG at Day 90	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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%.

Secondary Outcome Measures

Name	Time	Method
Forced Vital Capacity (FVC) at Day 90 Post-Transplantation	Day 90 post-transplantation	FVC at Day 90 post-transplantation is reported.
Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Baseline, Days 4, 8, 20 and 90 post-transplantation	iATP was expressed in ng/mL.
Percent of Predicted FEV1 at Day 90 Post-Transplantation	Day 90 post-transplantation	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Percent predicted FEV1 \[%\] = (FEV1 \[L\] / Predicted normal value FEV1 \[L\]) \* 100%
Change From Baseline in T-Cell Phenotype	Baseline, Days 20 and 90 post-transplantation	Reported values are change in the T-cell phenotype status from baseline to Day 20 and 90 for cluster of differentiation (CD) 3, CD19, CD4, CD4CD25, CD28, CD45RA, CD45RO, CD69, CD127, and CD152.
Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation	Day 90 post-transplantation	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Percentage of Participants With Opportunistic Infections	Up to Day 90	Opportunistic infections included all infections which occurred due to aspergillus, candida, pneumocystis, cryptococcus, listeria, herpes zoster, herpes simplex, cytomegalovirus pathogens.