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

Pharmacokinetics of Mycophenolate Mofetil in de Novo Lung Allograft Recipients

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.

Study Overview

• Status: Completed
• Conditions: Lung Transplantation
• Intervention / Treatment: Drug: mycophenolate mofetil

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Department of Cardiothoracic, Transplantation and Vascular Surgery at Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: mycophenolate mofetil; 1.5 g PO BID from Days 2 to 30 post-transplantation, 1 g PO BID Days 31 to 90 post-transplantation; Other Names: CellCept
Experimental: 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.	Drug: mycophenolate mofetil; 1.5 g PO BID from Days 2 to 30 post-transplantation, 1 g PO BID Days 31 to 90 post-transplantation; Other Names: CellCept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	Cmax was expressed in milligrams per liter (mg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 after transplantation
Cmax of MPA, MPAG and AcMPAG at Day 8	Cmax was expressed in mg/L.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Cmax of MPA, MPAG and AcMPAG at Day 20	Cmax was expressed in mg/L.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Cmax of MPA, MPAG and AcMPAG at Day 90	Cmax was expressed in mg/L.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Cmax of Free MPA at Day 4	Cmax was expressed in micrograms per liter (mcg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Cmax of Free MPA at Day 8	Cmax was expressed in mcg/L.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Cmax of Free MPA at Day 20	Cmax was expressed in mcg/L.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Cmax of Free MPA at Day 90	Cmax was expressed in mcg/L.	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 of MPA, MPAG, AcMPAG and Free MPA at Day 4	Dose-normalized Cmax was determined (in 1 per liter [1/L]) by dividing the Cmax by the actual dose taken.	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 of MPA, MPAG, AcMPAG and Free MPA at Day 8	Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.	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 of MPA, MPAG, AcMPAG and Free MPA at Day 20	Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.	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 of MPA, MPAG, AcMPAG and Free MPA at Day 90	Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
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 8		Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
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
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
Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	Cmin was expressed in mg/L.	Predose (0 hour) on Day 4 post-transplantation
Cmin of MPA, MPAG and AcMPAG at Day 8	Cmin was expressed in mg/L.	Predose (0 hour) on Day 8 post-transplantation
Cmin of MPA, MPAG and AcMPAG at Day 20	Cmin was expressed in mg/L.	Predose (0 hour) on Day 20 post-transplantation
Cmin of MPA, MPAG and AcMPAG at Day 90	Cmin was expressed in mg/L.	Predose (0 hour) on Day 90 post-transplantation
Cmin of Free MPA at Day 4	Cmin was expressed in mcg/L.	Predose (0 hour) on Day 4 post-transplantation
Cmin of Free MPA at Day 8	Cmin was expressed in mcg/L.	Predose (0 hour) on Day 8 post-transplantation
Cmin of Free MPA at Day 20	Cmin was expressed in mcg/L.	Predose (0 hour) on Day 20 post-transplantation
Cmin of Free MPA at Day 90	Cmin was expressed in mcg/L.	Predose (0 hour) on Day 90 post-transplantation
Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Vz of MPA, MPAG and AcMPAG at Day 8	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Vz of MPA, MPAG and AcMPAG at Day 20	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Vz of MPA, MPAG and AcMPAG at Day 90	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	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).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
CL of MPA, MPAG and AcMPAG at Day 8	CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
CL of MPA, MPAG and AcMPAG at Day 20	CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
CL of MPA, MPAG and AcMPAG at Day 90	CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	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]).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
AUC0-12 of MPA, MPAG and AcMPAG at Day 8	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
AUC0-12 of MPA, MPAG and AcMPAG at Day 20	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
AUC0-12 of MPA, MPAG and AcMPAG at Day 90	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
AUC0-12 of Free MPA at Day 4	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]).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
AUC0-12 of Free MPA at Day 8	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mcg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
AUC0-12 of Free MPA at Day 20	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mcg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
AUC0-12 of Free MPA at Day 90	AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours*(mcg/L).	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	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.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Free Fraction of Free MPA at Day 4	MPA Free fraction (in percent [%]) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
Free Fraction of Free MPA at Day 8	MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
Free Fraction of Free MPA at Day 20	MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
Free Fraction of Free MPA at Day 90	MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.	Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) at 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.	Day 90 post-transplantation
Percent of Predicted FEV1 at 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%	Day 90 post-transplantation
Forced Vital Capacity (FVC) at Day 90 Post-Transplantation	FVC at Day 90 post-transplantation is reported.	Day 90 post-transplantation
Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	iATP was expressed in ng/mL.	Baseline, Days 4, 8, 20 and 90 post-transplantation
Change From Baseline in T-Cell Phenotype	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.	Baseline, Days 20 and 90 post-transplantation
Percentage of Participants With Opportunistic Infections	Opportunistic infections included all infections which occurred due to aspergillus, candida, pneumocystis, cryptococcus, listeria, herpes zoster, herpes simplex, cytomegalovirus pathogens.	Up to Day 90

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: November 16, 2009
• First Submitted That Met QC Criteria: November 16, 2009
• First Posted (Estimate): November 17, 2009

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: ML22608; 2009-012231-15