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

NCT01014442 | Completed Phase 3 Results

• 2 other identifiers: ML226082009-012231-15
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Transplantation

Outcome Measures

Primary Outcomes (48)

• 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 Outcomes (6)

• Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation

  Day 90 post-transplantation

• Percent of Predicted FEV1 at Day 90 Post-Transplantation

  Day 90 post-transplantation

• 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

• Change From Baseline in T-Cell Phenotype

  Baseline, Days 20 and 90 post-transplantation

Study Arms (2)

Mycophenolate Mofetil; Cystic Fibrosis

EXPERIMENTAL

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

Mycophenolate Mofetil; Other

EXPERIMENTAL

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

Interventions

mycophenolate mofetil DRUG

1.5 g PO BID from Days 2 to 30 post-transplantation, 1 g PO BID Days 31 to 90 post-transplantation

Also known as: CellCept

Mycophenolate Mofetil; Cystic Fibrosis; Mycophenolate Mofetil; Other

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

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

Hanover, 30625, Germany

Location

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 17, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: February 10, 2017
• Results First Posted: February 10, 2017

Record last verified: 2015-07

Locations

DE (1)