Clinical trial NCT01014442: A Study of Mycophenolate Mofetil (CellCept) in Lung Transplant Recipients
Official title: Pharmacokinetics of Mycophenolate Mofetil in de Novo Lung Allograft Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Transplantation
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-11-17
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 after transplantation
measure: Cmax of MPA, MPAG and AcMPAG at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Cmax of MPA, MPAG and AcMPAG at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Cmax of MPA, MPAG and AcMPAG at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Cmax of Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Cmax of Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Cmax of Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Cmax of Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4
timeFrame: Predose (0 hour) on Day 4 post-transplantation
measure: Cmin of MPA, MPAG and AcMPAG at Day 8
timeFrame: Predose (0 hour) on Day 8 post-transplantation
measure: Cmin of MPA, MPAG and AcMPAG at Day 20
timeFrame: Predose (0 hour) on Day 20 post-transplantation
measure: Cmin of MPA, MPAG and AcMPAG at Day 90
timeFrame: Predose (0 hour) on Day 90 post-transplantation
measure: Cmin of Free MPA at Day 4
timeFrame: Predose (0 hour) on Day 4 post-transplantation
measure: Cmin of Free MPA at Day 8
timeFrame: Predose (0 hour) on Day 8 post-transplantation
measure: Cmin of Free MPA at Day 20
timeFrame: Predose (0 hour) on Day 20 post-transplantation
measure: Cmin of Free MPA at Day 90
timeFrame: Predose (0 hour) on Day 90 post-transplantation
measure: Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Vz of MPA, MPAG and AcMPAG at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Vz of MPA, MPAG and AcMPAG at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Vz of MPA, MPAG and AcMPAG at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Clearance (CL) of MPA, MPAG and AcMPAG at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: CL of MPA, MPAG and AcMPAG at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: CL of MPA, MPAG and AcMPAG at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: CL of MPA, MPAG and AcMPAG at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: AUC0-12 of MPA, MPAG and AcMPAG at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: AUC0-12 of MPA, MPAG and AcMPAG at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: AUC0-12 of MPA, MPAG and AcMPAG at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: AUC0-12 of Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: AUC0-12 of Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: AUC0-12 of Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: AUC0-12 of Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
measure: Free Fraction of Free MPA at Day 4
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation
measure: Free Fraction of Free MPA at Day 8
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation
measure: Free Fraction of Free MPA at Day 20
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation
measure: Free Fraction of Free MPA at Day 90
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation
Secondary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation
timeFrame: Day 90 post-transplantation
measure: Percent of Predicted FEV1 at Day 90 Post-Transplantation
timeFrame: Day 90 post-transplantation
measure: Forced Vital Capacity (FVC) at Day 90 Post-Transplantation
timeFrame: Day 90 post-transplantation
measure: Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels
timeFrame: Baseline, Days 4, 8, 20 and 90 post-transplantation
measure: Change From Baseline in T-Cell Phenotype
timeFrame: Baseline, Days 20 and 90 post-transplantation
measure: Percentage of Participants With Opportunistic Infections
timeFrame: Up to Day 90
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Department of Cardiothoracic, Transplantation and Vascular Surgery at Hannover Medical School
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: