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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01014442
First received: November 16, 2009
Last updated: December 19, 2016
Last verified: July 2015
  Purpose
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.

Condition Intervention Phase
Lung Transplantation Drug: mycophenolate mofetil Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Mycophenolate Mofetil in de Novo Lung Allograft Recipients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

  • Cmax of MPA, MPAG and AcMPAG at Day 90 [ Time Frame: 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 [ Time Frame: 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).

  • Cmax of Free MPA at Day 8 [ Time Frame: 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.

  • Cmax of Free MPA at Day 20 [ Time Frame: 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 [ Time Frame: 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 4 [ Time Frame: 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.

  • Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8 [ Time Frame: 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.

  • Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20 [ Time Frame: 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.

  • Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90 [ Time Frame: 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.

  • Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Predose (0 hour) on Day 4 post-transplantation ]
    Cmin was expressed in mg/L.

  • Cmin of MPA, MPAG and AcMPAG at Day 8 [ Time Frame: Predose (0 hour) on Day 8 post-transplantation ]
    Cmin was expressed in mg/L.

  • Cmin of MPA, MPAG and AcMPAG at Day 20 [ Time Frame: Predose (0 hour) on Day 20 post-transplantation ]
    Cmin was expressed in mg/L.

  • Cmin of MPA, MPAG and AcMPAG at Day 90 [ Time Frame: Predose (0 hour) on Day 90 post-transplantation ]
    Cmin was expressed in mg/L.

  • Cmin of Free MPA at Day 4 [ Time Frame: Predose (0 hour) on Day 4 post-transplantation ]
    Cmin was expressed in mcg/L.

  • Cmin of Free MPA at Day 8 [ Time Frame: Predose (0 hour) on Day 8 post-transplantation ]
    Cmin was expressed in mcg/L.

  • Cmin of Free MPA at Day 20 [ Time Frame: Predose (0 hour) on Day 20 post-transplantation ]
    Cmin was expressed in mcg/L.

  • Cmin of Free MPA at Day 90 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

  • Vz of MPA, MPAG and AcMPAG at Day 20 [ Time Frame: 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.

  • Vz of MPA, MPAG and AcMPAG at Day 90 [ Time Frame: 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.

  • Clearance (CL) of MPA, MPAG and AcMPAG at Day 4 [ Time Frame: 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).

  • CL of MPA, MPAG and AcMPAG at Day 8 [ Time Frame: 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 [ Time Frame: 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.

  • CL of MPA, MPAG and AcMPAG at Day 90 [ Time Frame: 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.

  • Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4 [ Time Frame: 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]).

  • AUC0-12 of MPA, MPAG and AcMPAG at Day 8 [ Time Frame: 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 20 [ Time Frame: 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).

  • AUC0-12 of MPA, MPAG and AcMPAG at Day 90 [ Time Frame: 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).

  • AUC0-12 of Free MPA at Day 4 [ Time Frame: 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 [ Time Frame: 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).

  • AUC0-12 of Free MPA at Day 20 [ Time Frame: 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).

  • AUC0-12 of Free MPA at Day 90 [ Time Frame: 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).

  • Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4 [ Time Frame: 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 [ Time Frame: 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 20 [ Time Frame: 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 90 [ Time Frame: 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 [ Time Frame: 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 8 [ Time Frame: 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%.

  • Free Fraction of Free MPA at Day 20 [ Time Frame: 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 [ Time Frame: 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:
  • Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation [ Time Frame: 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 of Predicted FEV1 at Day 90 Post-Transplantation [ Time Frame: 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%

  • Forced Vital Capacity (FVC) at Day 90 Post-Transplantation [ Time Frame: Day 90 post-transplantation ]
    FVC at Day 90 post-transplantation is reported.

  • Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels [ Time Frame: Baseline, Days 4, 8, 20 and 90 post-transplantation ]
    iATP was expressed in ng/mL.

  • Change From Baseline in T-Cell Phenotype [ Time Frame: 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.

  • Percentage of Participants With Opportunistic Infections [ Time Frame: Up to Day 90 ]
    Opportunistic infections included all infections which occurred due to aspergillus, candida, pneumocystis, cryptococcus, listeria, herpes zoster, herpes simplex, cytomegalovirus pathogens.


Enrollment: 68
Study Start Date: January 2010
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: CellCept

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014442

Locations
Germany
Department of Cardiothoracic, Transplantation and Vascular Surgery at Hannover Medical School
Hannover, Germany, 30625
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01014442     History of Changes
Other Study ID Numbers: ML22608
2009-012231-15
Study First Received: November 16, 2009
Results First Received: December 19, 2016
Last Updated: December 19, 2016

Additional relevant MeSH terms:
Mycophenolic Acid
Mycophenolate mofetil
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2017